RAHWAY, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that new data for four approved medicines and six pipeline candidates in more than 20 types of cancer will be presented at the European Society for Medical Oncology (ESMO) Congress 2024 in Barcelona, Spain, from Sept.

新泽西州拉赫韦（商业新闻短讯）--默克（纽约证券交易所代码：MRK），在美国和加拿大以外被称为MSD，今天宣布，将于9月1日起在西班牙巴塞罗那举行的2024年欧洲肿瘤内科学会（ESMO）大会上提交20多种癌症的四种批准药物和六种候选药物的新数据。

13-17. Study findings from the Phase 3 KEYNOTE-522 trial (#LBA4) in high-risk early-stage triple-negative breast cancer (TNBC), the Phase 3 KEYNOTE-A18 trial (#709O) in high-risk locally advanced cervical cancer and the Phase 3 LEAP-012 trial (#LBA3) in unresectable, non-metastatic hepatocellular carcinoma, in collaboration with Eisai, have been selected for the ESMO Presidential Symposium Sessions.

13-17岁。高风险早期三阴性乳腺癌（TNBC）的3期KEYNOTE-522试验（#LBA4），高风险局部晚期宫颈癌的3期KEYNOTE-A18试验（#709O）和不可切除的非转移性肝细胞癌的3期LEAP-012试验（#LBA3）与Eisai合作的研究结果已被选入ESMO总统研讨会。

Data being shared at the Congress showcase the company’s continued progress in advancing clinical research for Merck’s broad portfolio and diverse pipeline of investigational candidates, with a total of 80 abstracts being presented..

大会上分享的数据展示了该公司在推进默克公司广泛的投资组合和多样化的研究候选人的临床研究方面取得的持续进展，总共提交了80篇摘要。。

“Over the past decade, data on KEYTRUDA have contributed to paradigm shifts in the treatment of some of the deadliest forms of cancer and the rewriting of medical textbooks. We are very proud that today marks ten years since KEYTRUDA received its first approval in the U.S.,” said Dr. Eliav Barr, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories.

默克研究实验室首席医学官、高级副总裁兼全球临床开发主管Eliav Barr博士说：“过去十年来，KEYTRUDA的数据推动了一些最致命癌症治疗的范式转变和医学教科书的重写。今天是KEYTRUDA在美国首次获得批准的十年，我们感到非常骄傲。”。

“The compelling data for KEYTRUDA at this year’s ESMO are demonstrative of KEYTRUDA’s impressive journey, from 10-year survival data in unresectable or metastatic melanoma to new overall survival data in earlier stages of two types of women’s cancers. We’re also excited to show how we’re building on our leadership in oncology with data from our broad and diverse pipeline as we work toward improved outcomes for as many patients as possible.”.

“KEYTRUDA在今年的ESMO上获得的令人信服的数据表明了KEYTRUDA令人印象深刻的历程，从不可切除或转移性黑色素瘤的10年生存数据到两种女性癌症早期的新总体生存数据。我们也很兴奋地展示我们如何利用我们广泛多样的渠道数据建立我们在肿瘤学方面的领导地位，同时我们努力改善尽可能多的患者的预后。”。

Presentations at the Congress will feature new or updated findings from Merck’s broad portfolio of cancer medicines: KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy; WELIREG® (belzutifan); LENVIMA® (lenvatinib), in collaboration with Eisai; and LYNPARZA® (olaparib), in collaboration with AstraZeneca..

大会上的演讲将介绍默克公司广泛的癌症药物组合的新发现或最新发现：KEYTRUDA®（pembrolizumab），默克公司的抗PD-1疗法；；LENVIMA®（lenvatinib），与Eisai合作；和LYNPARZA®（olaparib），与阿斯利康合作。。

Key data from Merck’s portfolio to be presented at ESMO Congress 2024:

默克公司投资组合的关键数据将在2024年ESMO大会上公布：

First-time overall survival (OS) results from the Phase 3 KEYNOTE-522 trial evaluating KEYTRUDA in combination with chemotherapy as neoadjuvant treatment and then continuing as single agent as adjuvant treatment in patients with high-risk early-stage TNBC (Presentation #LBA4; Presidential Symposium II: Practice-changing trials)..

第三阶段KEYNOTE-522试验的首次总生存期（OS）结果评估了KEYTRUDA联合化疗作为新辅助治疗，然后继续作为单一药物作为高危早期TNBC患者的辅助治疗（演讲#LBA4；总统研讨会II：实践改变试验）。。

OS data from the Phase 3 KEYNOTE-A18 trial evaluating KEYTRUDA in combination with concurrent chemoradiotherapy (CRT) as treatment for patients with high-risk locally advanced cervical cancer (Presentation #709O; Presidential Symposium I: Practice-changing trials).1

来自第三阶段KEYNOTE-A18试验的OS数据评估了KEYTRUDA联合同步放化疗（CRT）治疗高危局部晚期宫颈癌（演讲#709O；总统研讨会I：改变实践的试验）

First presentation of results from the first interim analysis of the Phase 3 LEAP-012 trial evaluating KEYTRUDA plus LENVIMA in combination with transarterial chemoembolization (TACE) in patients with unresectable, non-metastatic hepatocellular carcinoma (Presentation #LBA3; Presidential Symposium I: Practice-changing trials).2.

首次介绍了对不可切除的非转移性肝细胞癌患者评估KEYTRUDA加LENVIMA联合经动脉化疗栓塞（TACE）的3期LEAP-012试验的第一次中期分析结果（介绍#LBA3；总统研讨会I：实践改变试验）。

Ten-year OS data from the Phase 3 KEYNOTE-006 trial evaluating KEYTRUDA compared to ipilimumab as first-line treatment for patients with advanced melanoma (Presentation #LBA44; Mini oral session: Melanoma and other skin tumours).

来自第三阶段KEYNOTE-006试验的十年OS数据评估了KEYTRUDA与ipilimumab相比作为晚期黑色素瘤患者的一线治疗（介绍#LBA44；小型口腔治疗：黑色素瘤和其他皮肤肿瘤）。

OS data from the per protocol final analysis of the Phase 3 KEYNOTE-811 trial evaluating KEYTRUDA plus trastuzumab and chemotherapy as first-line treatment for patients with advanced human epidermal growth factor receptor 2 (HER2)-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma (Presentation #1400O; Proffered paper session 2: GI tumours, upper digestive)..

OS数据来自第3阶段KEYNOTE-811试验的按方案最终分析，该试验评估了KEYTRUDA加曲妥珠单抗和化疗作为晚期人类表皮生长因子受体2（HER2）阳性胃或胃食管交界处（GEJ）腺癌患者的一线治疗（演讲#14000；提交的论文第2次会议：胃肠道肿瘤，上消化道）。。

Data from the per protocol final analysis of the Phase 3 LITESPARK-005 trial evaluating WELIREG as treatment for adult patients with advanced renal cell carcinoma that progressed following PD-1/L1 inhibitor and vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI) therapies (Presentation #LBA74; Proffered paper session 1: GU tumours, non-prostate)..

来自3期LITESPARK-005试验的每个方案最终分析的数据，该试验评估了WELIREG作为PD-1/L1抑制剂和血管内皮生长因子酪氨酸激酶抑制剂（VEGF-TKI）治疗后进展的晚期肾细胞癌成年患者的治疗（介绍#LBA74；提交的论文第1部分：GU肿瘤，非前列腺癌）。。

Additionally, new data on investigational candidates from Merck’s pipeline will be presented at the Congress, including for: patritumab deruxtecan (HER3-DXd), a HER3-directed antibody-drug conjugate (ADC), and ifinatamab deruxtecan (I-DXd; also known as MK-2400) being developed in collaboration with Daiichi Sankyo; sacituzumab tirumotecan (sac-TMT; also known as MK-2870/SKB264), an investigational anti-TROP2 ADC being developed in collaboration with Kelun-Biotech; and opevesostat (also known as MK-5684/ODM-208), an investigational steroid synthesis inhibitor in collaboration with Orion..

此外，默克公司管道研究候选人的新数据将在大会上提交，包括：patritumab deruxtecan（HER3 DXd），HER3定向抗体药物偶联物（ADC）和ifinatamab deruxtecan（I-DXd；也称为MK-2400）正在与第一三共合作开发；sacituzumab tirumotecan（sac TMT；也称为MK-2870/SKB264），一种与科伦生物技术公司合作开发的研究性抗TROP2 ADC；和opevesostat（也称为MK-5684/ODM-208），一种与猎户座合作的研究性类固醇合成抑制剂。。

Key data on investigational candidates from Merck’s pipeline to be presented at ESMO Congress 2024:

将在2024年ESMO大会上提交的默克管道研究候选人的关键数据：

Data from the Phase 2 ICARUS-BREAST01 trial evaluating HER3-DXd as treatment for patients with hormone-receptor (HR)-positive/HER2-negative advanced breast cancer (Presentation #340O; Proffered paper session: Breast cancer, metastatic).3

来自2期ICARUS-BREAST01试验的数据评估HER3 DXd治疗激素受体（HR）阳性/HER2阴性晚期乳腺癌患者（介绍#340O；提供的论文会议：乳腺癌，转移性）

First-time data from a Phase 2 study conducted in China, independently led by Kelun-Biotech, evaluating sac-TMT as treatment for patients with previously treated advanced endometrial carcinoma and ovarian cancer (Presentation #715MO; Mini oral session 2: Gynaecological cancers).4

科伦生物技术公司（Kelun Biotech）独立领导的在中国进行的第二阶段研究的首次数据，评估sac TMT治疗先前治疗的晚期子宫内膜癌和卵巢癌患者（演示#715MO；小型口腔会议2：妇科癌症）

Findings from a Phase 2 study conducted in China, independently led by Kelun-Biotech, evaluating sac-TMT plus KEYTRUDA as treatment for patients with recurrent or metastatic cervical cancer (Presentation #716MO; Mini oral session 2: Gynaecological cancers).4

科伦生物技术公司（Kelun Biotech）独立领导的在中国进行的一项2期研究的结果，评估了sac TMT加KEYTRUDA治疗复发或转移性宫颈癌患者（介绍#716MO；小型口腔会议2：妇科癌症）

Details on abstracts listed above and additional key abstracts for Merck

上面列出的摘要的详细信息以及默克公司的其他关键摘要

Breast cancer

乳腺癌

Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for high-risk early-stage TNBC: Overall survival results from the Phase 3 KEYNOTE-522 study. P. Schmid.

新辅助pembrolizumab或安慰剂加化疗，然后辅助pembrolizumab或安慰剂治疗高危早期TNBC：3期KEYNOTE-522研究的总生存率结果。P、 施密德。

Presentation #LBA4, Presidential Symposium II: Practice-changing trials

演讲#LBA4，总统研讨会II：改变实践的试验

Efficacy, safety and biomarker analysis of ICARUS-BREAST01: a Phase 2 Study of Patritumab Deruxtecan (HER3-DXd), in patients (pts) with HR+/HER2- advanced breast cancer (ABC). B. Pistilli.3

ICARUS-BREAST01的疗效，安全性和生物标志物分析：Patritumab Deruxtecan（HER3 DXd）在HR+/HER2晚期乳腺癌（ABC）患者（pts）中的2期研究。B、 雌蕊3

Presentation #340O, Proffered paper session: Breast cancer, metastatic

演讲#340O，提供的论文会议：乳腺癌，转移性

Intensified alkylating chemotherapy with autologous stem cell rescue (IACT) or conventional chemotherapy followed by olaparib (CCT-O) in stage III, HER2-negative, homologous recombination deficient (HRD) breast cancer (BC): Survival results of the randomized-controlled SUBITO trial. S. Linn.5

在III期，HER2阴性，同源重组缺陷（HRD）乳腺癌（BC）中，用自体干细胞拯救（IACT）或常规化疗进行强化烷化化疗，然后使用奥拉帕尼（CCT-O）：随机对照SUBITO试验的生存结果。S、 第5行

Presentation #LBA14, Mini oral session: Breast cancer, early stage

演讲#LBA14，小型口腔会议：乳腺癌，早期

Gastrointestinal cancers

Transarterial Chemoembolization (TACE) With or Without Lenvatinib (len) + Pembrolizumab (pembro) for Intermediate-Stage Hepatocellular Carcinoma (HCC): Phase 3 LEAP-012 Study. J. Llovet.2

有或没有Lenvatinib（len）+Pembrolizumab（pembro）的经动脉化疗栓塞（TACE）治疗中期肝细胞癌（HCC）：3期LEAP-012研究。J、 第2部分

Presentation #LBA3, Presidential Symposium I: Practice-changing trials

演讲#LBA3，总统研讨会I：改变实践的试验

Final overall survival for the Phase 3, KEYNOTE-811 study of pembrolizumab plus trastuzumab and chemotherapy for HER2+ advanced, unresectable or metastatic G/GEJ adenocarcinoma. S. Lonardi.

pembrolizumab联合曲妥珠单抗和HER2+晚期，不可切除或转移性G/GEJ腺癌化疗的3期KEYNOTE-811研究的最终总生存期。S、 洛纳迪。

Presentation #1400O, Proffered paper session 2: GI tumours, upper digestive

演讲#14000，提交的论文第2课：胃肠道肿瘤，上消化道

Genitourinary cancers

泌尿生殖系统癌症

Final analysis of the Phase 3 LITESPARK-005 study of belzutifan versus everolimus in participants (pts) with previously treated advanced clear cell renal cell carcinoma (ccRCC). B. I. Rini.

belzutifan与依维莫司在先前治疗的晚期透明细胞肾细胞癌（ccRCC）参与者（pts）中的3期LITESPARK-005研究的最终分析。B、 。

Presentation #LBA74, Proffered paper session 1: GU tumours, non-prostate

演讲#LBA74，提交的论文第1部分：非前列腺GU肿瘤

Opevesostat (MK-5684/ODM-208), an oral CYP11A1 inhibitor, in metastatic castration-resistant prostate cancer (mCRPC): updated CYPIDES Phase 2 results. K. Fizazi.6

口服CYP11A1抑制剂Opevesostat（MK-5684/ODM-208）治疗转移性去势抵抗性前列腺癌（mCRPC）：更新CYPIDES 2期结果。K、 菲扎齐6

Presentation #1605P, Poster

演示文稿#1605P，海报

Alliance A031501: AMBASSADOR Study of Adjuvant Pembrolizumab (Pembro) in Muscle-Invasive Urothelial Carcinoma (MIUC) vs Observation (Obs): Extended follow-up disease-free survival (DFS) results and metastatic (met) disease recurrence distribution. A. B. Apolo.7

联盟A031501：肌肉浸润性尿路上皮癌（MIUC）与观察（Obs）中辅助Pembrolizumab（Pembro）的大使研究：延长随访无病生存期（DFS）结果和转移性（met）疾病复发分布。A、 B.阿波罗7

Presentation #1964MO, Mini oral session: GU tumours, non-prostate

介绍#1964MO，小型口腔会议：GU肿瘤，非前列腺

Study EV-103 Dose Escalation/Cohort A (DE/A): 5y Follow-Up Of First-Line (1L) Enfortumab Vedotin (EV) + Pembrolizumab (P) in Cisplatin (cis)-Ineligible Locally Advanced Or Metastatic Urothelial Carcinoma (la/mUC). J. E. Rosenberg.8

研究EV-103剂量递增/队列A（DE/A）：顺铂（cis）-不合格的局部晚期或转移性尿路上皮癌（la/mUC）中一线（1L）Enfortumab Vedotin（EV）+Pembrolizumab（P）的5年随访。J、 罗森博格8

Presentation #1968P, Poster

演示文稿#1968P，海报

Preliminary Efficacy And Safety Of Disitamab Vedotin (DV) With Pembrolizumab (P) In Treatment (Tx)-Naive HER2-Expressing, Locally Advanced Or Metastatic Urothelial Carcinoma (la/mUC): RC48G001 Cohort C. M. D. Galsky.8

地西他单抗Vedotin（DV）与Pembrolizumab（P）联合治疗（Tx）-未表达HER2的局部晚期或转移性尿路上皮癌（la/mUC）的初步疗效和安全性：RC48G001队列C.M.D.Galsky。8

Presentation #1967MO, Mini oral session: GU tumours, non-prostate

演示#1967MO，小型口腔会议：GU肿瘤，非前列腺

Gynecologic cancers

妇科癌症

Pembrolizumab plus chemoradiotherapy for high-risk locally advanced cervical cancer: Overall survival results from the randomized, double-blind, Phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study. D. Lorusso.1

。D、 洛鲁索1

Presentation #709O, Presidential Symposium I: Practice-changing trials

演讲#709O，总统研讨会I：改变实践的试验

Safety and Efficacy of Sacituzumab Tirumotecan (sac-TMT) in Patients (pts) with Previously Treated Advanced Endometrial Carcinoma (EC) and Ovarian Cancer (OC) from a Phase 2 Study. D. Wang.4

Sacituzumab Tirumotecan（sac TMT）在2期研究中对先前治疗的晚期子宫内膜癌（EC）和卵巢癌（OC）患者（pts）的安全性和有效性。D、 王。4

Presentation #715MO, Mini oral session 2: Gynaecological cancers

演示#715MO，迷你口腔课程2：妇科癌症

Efficacy and Safety of Sacituzumab Tirumotecan (sac-TMT) Plus Pembrolizumab in Patients with Recurrent or Metastatic Cervical Cancer. X. Wu.4

Sacituzumab Tirumotecan（sac TMT）联合Pembrolizumab治疗复发或转移性宫颈癌患者的疗效和安全性。十、 吴。4

Presentation #716MO, Mini oral session 2: Gynaecological cancers

演示#716MO，迷你口腔课程2：妇科癌症

Lung cancer

肺癌

Neoadjuvant Pembrolizumab (pembro) or Placebo (pbo) Plus Chemotherapy and Adjuvant Pembro or Pbo for Early-Stage NSCLC: Subgroup Analyses of the Phase 3 KEYNOTE-671 Study. M. C. Garassino.

新辅助Pembrolizumab（pembro）或安慰剂（pbo）加化疗和辅助pembro或pbo治疗早期NSCLC：3期KEYNOTE-671研究的亚组分析。M、 C.加拉西诺。

Presentation #1210P, Poster

演示文稿#1210P，海报

Ifinatamab deruxtecan (I-DXd; DS-7300) in patients with advanced solid tumors: Updated clinical and biomarker results from a phase I/II study. M. R. Patel. 3

晚期实体瘤患者的Ifinatamab deruxtecan（I-DXd；DS-7300）：I/II期研究的最新临床和生物标志物结果。M、 R.帕特尔。3

Presentation #690P, Poster

演示文稿#690P，海报

Melanoma and other skin cancers

黑色素瘤和其他皮肤癌

Pembrolizumab vs Ipilimumab in Advanced Melanoma: 10-Year Follow-Up of the Phase 3 KEYNOTE-006 Study. C. Robert

Pembrolizumab与Ipilimumab治疗晚期黑色素瘤：3期KEYNOTE-006研究的10年随访。C、 罗伯特

Presentation #LBA44, Mini oral session: Melanoma and other skin tumours

Pembrolizumab versus placebo after a complete resection of high-risk stage III melanoma: 7-year results of the EORTC 1325-MG/Keynote-054 double-blind Phase 3 trial. A. M. Eggermont.

在完全切除高危III期黑色素瘤后，Pembrolizumab与安慰剂：EORTC 1325-MG/Keynote-054双盲3期试验的7年结果。A、 M.Eggermont。

Presentation #1095P, Poster

演示文稿#1095P，海报

KEYMAKER-U02 substudy 02C: neoadjuvant pembrolizumab (pembro) and investigational agents followed by adjuvant pembro for stage IIIB-D melanoma. G. V. Long.

KEYMAKER-U02子研究02C：新辅助pembrolizumab（pembro）和研究药物，然后是辅助pembro治疗IIIB-D期黑色素瘤。G、 V.长。

Presentation #1082O, Proffered paper session: Melanoma and other skin tumours

演讲#1082O，提供的论文会议：黑色素瘤和其他皮肤肿瘤

Pembrolizumab (pembro) vs placebo as adjuvant therapy for high-risk stage II melanoma: Long-term follow-up, rechallenge, and crossover in KEYNOTE-716. J. J. Luke.

Pembrolizumab（pembro）与安慰剂作为高危II期黑色素瘤的辅助治疗：KEYNOTE-716中的长期随访，再次挑战和交叉。J、 J.卢克。

Presentation #1078MO, Mini oral session: Melanoma and other skin tumours

演示#1078MO，小型口腔会议：黑色素瘤和其他皮肤肿瘤

KEYMAKER 02B: A randomized trial of pembrolizumab (pembro) alone or with investigational agents as first-line treatment for advanced melanoma. R. Dummer.

KEYMAKER 02B：pembrolizumab（pembro）单独或与研究药物联合作为晚期黑色素瘤一线治疗的随机试验。R、 达默。

Presentation #1083P, Poster

演示文稿#1083P，海报

Primary Results from TACTI-003: A Randomized Phase IIb Trial Comparing Eftilagimod Alpha (soluble LAG-3) Plus Pembrolizumab Versus Pembrolizumab Alone in First-Line Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with CPS ≥1. C. A. Kristensen.9

TACI-003的主要结果：一项随机IIb期试验，比较了依替拉莫德α（可溶性LAG-3）加Pembrolizumab与单独使用Pembrolizumab治疗CPS≥1的一线复发或转移性头颈部鳞状细胞癌。C、 A.克里斯滕森9

Presentation #LBA35, Proffered paper session: Head and neck cancer

演讲#LBA35，提交的论文会议：头颈部癌症

1 In collaboration with the European Network for Gynaecological Oncology Trial (ENGOT) groups and the GOG Foundation, Inc. (GOG)

1与欧洲妇科肿瘤试验网络（ENGOT）小组和GOG基金会（GOG）合作

2 In collaboration with Eisai

2与卫材合作

3 In collaboration with Daiichi Sankyo

3与第一三共合作

4 Independent study led by Kelun-Biotech

科伦生物技术公司领导的4项独立研究

5 In collaboration with AstraZeneca

5与阿斯利康合作

6 In collaboration with Orion Pharma

6与Orion Pharma合作

7 Sponsored by U.S. National Cancer Institute (NCI)/led by Alliance for Clinical Trials in Oncology

7由美国国家癌症研究所（NCI）赞助/由肿瘤学临床试验联盟领导

8 In collaboration with Astellas/Pfizer

8与Astellas/辉瑞合作

9 In collaboration with Immutep

9与Immutep合作

About Merck’s early-stage cancer clinical program

关于默克公司的早期癌症临床计划

Finding cancer at an earlier stage may give patients a greater chance of long-term survival. Many cancers are considered most treatable and potentially curable in their earliest stage of disease. Building on the strong understanding of the role of KEYTRUDA in later-stage cancers, Merck is evaluating our portfolio of medicines and pipeline candidates in earlier disease states, with more than 30 ongoing registrational studies across multiple types of cancer..

在早期发现癌症可能会使患者获得更大的长期生存机会。许多癌症在疾病的早期阶段被认为是最可治疗和可能治愈的。基于对KEYTRUDA在晚期癌症中的作用的深刻理解，默克公司正在评估我们在早期疾病状态下的药物和候选药物组合，目前正在进行30多项针对多种癌症的注册研究。。

About KEYTRUDA® (pembrolizumab) injection, 100 mg

关于KEYTRUDA®（pembrolizumab）注射液，100 mg

KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells..

。KEYTRUDA是一种人源化单克隆抗体，可阻断PD-1及其配体PD-L1和PD-L2之间的相互作用，从而激活可能影响肿瘤细胞和健康细胞的T淋巴细胞。。

Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers..

默克公司拥有业界最大的免疫肿瘤学临床研究项目。目前有1600多项试验研究了KEYTRUDA在各种癌症和治疗环境中的作用。。。

Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.

美国选定的KEYTRUDA®（pembrolizumab）适应症。

Melanoma

黑色素瘤

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA适用于治疗不可切除或转移性黑色素瘤患者。

KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with Stage IIB, IIC, or III melanoma following complete resection.

KEYTRUDA适用于完全切除后IIB，IIC或III期黑色素瘤的成人和儿科（12岁及以上）患者的辅助治疗。

Non-Small Cell Lung Cancer

非小细胞肺癌

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA联合培美曲塞和铂类化疗可用于转移性非鳞状非小细胞肺癌（NSCLC）患者的一线治疗，无EGFR或ALK基因组肿瘤畸变。

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA联合卡铂和紫杉醇或紫杉醇蛋白结合，适用于转移性鳞状NSCLC患者的一线治疗。

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [Tumor Proportion Score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:

Stage III where patients are not candidates for surgical resection or definitive chemoradiation, or

第三阶段，患者不适合手术切除或确定性放化疗，或

metastatic.

转移性。

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA..

KEYTRUDA作为单一药物，用于治疗转移性NSCLC患者，其肿瘤表达PD-L1（TPS≥1%），通过FDA批准的测试确定，在含铂化疗时或之后疾病进展。患有EGFR或ALK基因组肿瘤畸变的患者在接受KEYTRUDA之前，应在FDA批准的这些畸变治疗中取得疾病进展。。

KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.

KEYTRUDA适用于可切除（肿瘤≥4 cm或淋巴结阳性）NSCLC患者联合含铂化疗作为新辅助治疗，然后在手术后继续作为单一药物作为辅助治疗。

KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC.

KEYTRUDA作为单一药物，被指定为IB期（T2a≥4 cm），II期或IIIA期NSCLC成年患者切除和铂类化疗后的辅助治疗。

Urothelial Cancer

尿路上皮癌

KEYTRUDA, in combination with enfortumab vedotin, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer.

KEYTRUDA与enfortumab vedotin联合用于治疗局部晚期或转移性尿路上皮癌的成年患者。

KEYTRUDA, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma:

KEYTRUDA作为单一药物，适用于治疗局部晚期或转移性尿路上皮癌患者：

who are not eligible for any platinum-containing chemotherapy, or

不符合任何含铂化疗的资格，或

who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

在含铂化疗期间或之后，或在新辅助治疗或含铂化疗辅助治疗后12个月内出现疾病进展的患者。

KEYTRUDA, as a single agent, is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy..

KEYTRUDA作为单一药物，适用于治疗卡介苗（BCG）无反应，高风险，非肌肉浸润性膀胱癌（NMIBC）患者，伴有或不伴有乳头状肿瘤的原位癌（CIS），这些患者不符合或选择不进行膀胱切除术。。

Gastric Cancer

胃癌

KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test..

KEYTRUDA联合曲妥珠单抗，含氟嘧啶和铂类化疗，适用于局部晚期不可切除或转移性HER2阳性胃或胃食管交界处（GEJ）腺癌患者的一线治疗，其肿瘤表达PD-L1（CPS≥1），由FDA批准的测试确定。。

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval of this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

根据肿瘤反应率和反应持久性，该适应症在加速批准下获得批准。。

KEYTRUDA, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.

KEYTRUDA联合含氟嘧啶和铂的化疗，适用于局部晚期不可切除或转移性HER2阴性胃或胃食管连接（GEJ）腺癌的成人一线治疗。

Cervical Cancer

宫颈癌

KEYTRUDA, in combination with chemoradiotherapy (CRT), is indicated for the treatment of patients with FIGO 2014 Stage III-IVA cervical cancer.

KEYTRUDA联合放化疗（CRT）用于治疗FIGO 2014 III-IVA期宫颈癌患者。

KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.

KEYTRUDA联合化疗，有或没有贝伐单抗，适用于治疗持续性，复发性或转移性宫颈癌患者，其肿瘤表达PD-L1（CPS≥1），由FDA批准的测试确定。

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.

KEYTRUDA作为单一药物，用于治疗复发性或转移性宫颈癌患者，其肿瘤表达PD-L1（CPS≥1），通过FDA批准的测试确定，其在化疗时或化疗后疾病进展。

Hepatocellular Carcinoma

肝细胞癌

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) secondary to hepatitis B who have received prior systemic therapy other than a PD-1/PD-L1-containing regimen.

KEYTRUDA适用于治疗继发于乙型肝炎的肝细胞癌（HCC）患者，这些患者先前接受过除含PD-1/PD-L1方案以外的全身治疗。

Cutaneous Squamous Cell Carcinoma

皮肤鳞状细胞癌

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.

KEYTRUDA适用于治疗复发或转移性皮肤鳞状细胞癌（cSCC）或局部晚期cSCC患者，这些患者无法通过手术或放疗治愈。

Triple-Negative Breast Cancer

三阴性乳腺癌

KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.

KEYTRUDA适用于治疗高危早期三阴性乳腺癌（TNBC）患者，联合化疗作为新辅助治疗，然后在手术后继续作为单一药物作为辅助治疗。

KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.

KEYTRUDA联合化疗用于治疗局部复发的不可切除或转移性TNBC患者，其肿瘤表达PD-L1（CPS≥10），这是由FDA批准的测试确定的。

See additional selected KEYTRUDA indications in the U.S. after the Selected Important Safety Information.

在选定的重要安全信息之后，请参阅美国的其他选定KEYTRUDA指示。

Selected Important Safety Information for KEYTRUDA

为KEYTRUDA选择的重要安全信息

Severe and Fatal Immune-Mediated Adverse Reactions

严重和致命的免疫介导的不良反应

KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or the programmed death ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions.

KEYTRUDA是一种单克隆抗体，属于一类与程序性死亡受体-1（PD-1）或程序性死亡配体1（PD-L1）结合的药物，阻断PD-1/PD-L1途径，从而消除对免疫反应的抑制，可能破坏外周耐受并诱导免疫介导的不良反应。

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions..

免疫介导的不良反应可能是严重或致命的，可能发生在任何器官系统或组织中，可能同时影响多个身体系统，并且可能在开始治疗或停止治疗后的任何时间发生。此处列出的重要免疫介导的不良反应可能不包括所有可能的严重和致命的免疫介导的不良反应。。

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of anti–PD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment.

密切监测患者的症状和体征，这些症状和体征可能是潜在的免疫介导的不良反应的临床表现。早期识别和管理对于确保安全使用抗PD-1/PD-L1治疗至关重要。在基线和治疗期间定期评估肝酶，肌酐和甲状腺功能。

For patients with TNBC treated with KEYTRUDA in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate..

对于在新辅助治疗中接受KEYTRUDA治疗的TNBC患者，在基线，手术前以及临床指示下监测血液皮质醇。在疑似免疫介导的不良反应的情况下，启动适当的检查以排除其他病因，包括感染。及时进行医疗管理，包括适当的专业咨询。。

Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month.

根据免疫介导的不良反应的严重程度，扣留或永久停用KEYTRUDA。一般来说，如果KEYTRUDA需要中断或停药，则给予全身皮质类固醇治疗（1至2 mg/kg/天泼尼松或等效药物），直到改善至1级或更低。在改善至1级或更低级别后，开始逐渐减少皮质类固醇，并在至少1个月内继续逐渐减少。

Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy..

考虑在皮质类固醇治疗无法控制不良反应的患者中使用其他全身免疫抑制剂。。

Immune-Mediated Pneumonitis

免疫介导性肺炎

KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions.

KEYTRUDA可引起免疫介导的肺炎。接受过胸部放疗的患者发病率较高。接受KEYTRUDA治疗的患者中有3.4%（94/2799）发生免疫介导的肺炎，包括致命（0.1%），4级（0.3%），3级（0.9%）和2级（1.3%）反应。

Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients..

67%（63/94）的患者需要全身皮质类固醇。肺炎导致1.3%（36）的患者永久停止使用KEYTRUDA，0.9%（26）的患者停止使用KEYTRUDA。；其中23%复发。94名患者中有59%的肺炎得到了缓解。。

Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation.

。患者接受大剂量皮质类固醇治疗，中位持续时间为10天（范围：2天至53个月）。既往有无胸部放疗的患者肺炎发生率相似。

Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution..

。在发生肺炎的患者中，42%的患者中断了KEYTRUDA，68%的患者停止了KEYTRUDA，77%的患者已经解决。。

Pneumonitis occurred in 7% (41/580) of adult patients with resected NSCLC who received KEYTRUDA as a single agent for adjuvant treatment of NSCLC, including fatal (0.2%), Grade 4 (0.3%), and Grade 3 (1%) adverse reactions. Patients received high-dose corticosteroids for a median duration of 10 days (range: 1 day to 2.3 months).

接受KEYTRUDA作为单一药物辅助治疗NSCLC的成年NSCLC患者中有7%（41/580）发生肺炎，包括致命（0.2%），4级（0.3%）和3级（1%）不良反应。患者接受大剂量皮质类固醇治疗，中位持续时间为10天（范围：1天至2.3个月）。

Pneumonitis led to discontinuation of KEYTRUDA in 26 (4.5%) of patients. Of the patients who developed pneumonitis, 54% interrupted KEYTRUDA, 63% discontinued KEYTRUDA, and 71% had resolution..

肺炎导致26名（4.5%）患者停用KEYTRUDA。在发生肺炎的患者中，54%的患者中断了KEYTRUDA，63%的患者停止了KEYTRUDA，71%的患者已经解决。。

Immune-Mediated Colitis

免疫介导的结肠炎

KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.

KEYTRUDA可引起免疫介导的结肠炎，可能伴有腹泻。据报道，皮质类固醇难治性免疫介导的结肠炎患者的巨细胞病毒感染/再激活。在皮质类固醇难治性结肠炎的情况下，考虑重复感染性检查以排除其他病因。

Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids were required in 69% (33/48); additional immunosuppressant therapy was required in 4.2% of patients. Colitis led to permanent discontinuation of KEYTRUDA in 0.5% (15) and withholding in 0.5% (13) of patients.

接受KEYTRUDA治疗的患者中有1.7%（48/2799）发生免疫介导的结肠炎，包括4级（<0.1%），3级（1.1%）和2级（0.4%）反应。69%（33/48）需要全身皮质类固醇；4.2%的患者需要额外的免疫抑制剂治疗。结肠炎导致0.5%（15）的患者永久停止使用KEYTRUDA，0.5%（13）的患者停止使用KEYTRUDA。

All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Colitis resolved in 85% of the 48 patients..

；其中23%复发。48名患者中有85%的结肠炎消退。。

Hepatotoxicity and Immune-Mediated Hepatitis

肝毒性和免疫介导的肝炎

KEYTRUDA as a Single Agent

KEYTRUDA作为单一代理人

KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 68% (13/19) of patients; additional immunosuppressant therapy was required in 11% of patients.

KEYTRUDA可引起免疫介导的肝炎。接受KEYTRUDA治疗的患者中有0.7%（19/2799）发生免疫介导的肝炎，包括4级（<0.1%），3级（0.4%）和2级（0.1%）反应。68%（13/19）的患者需要全身皮质类固醇；11%的患者需要额外的免疫抑制剂治疗。

Hepatitis led to permanent discontinuation of KEYTRUDA in 0.2% (6) and withholding in 0.3% (9) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Hepatitis resolved in 79% of the 19 patients..

肝炎导致0.2%（6）的患者永久停用KEYTRUDA，0.3%（9）的患者停用KEYTRUDA。；其中，没有人复发。19名患者中有79%的肝炎消退。。

KEYTRUDA With Axitinib

KEYTRUDA与Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed.

KEYTRUDA联合阿西替尼可引起肝毒性。在开始治疗之前和整个治疗过程中定期监测肝酶。与药物作为单一药物给药相比，考虑更频繁地监测。对于肝酶升高，中断KEYTRUDA和axitinib，并考虑根据需要服用皮质类固醇。

With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST) (13%) were seen at a higher frequency compared to KEYTRUDA alone. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids.

与单独使用KEYTRUDA相比，联合使用KEYTRUDA和axitinib后，3级和4级丙氨酸转氨酶（ALT）升高（20%）和天冬氨酸转氨酶（AST）升高（13%）的频率更高。ALT升高的患者中有59%接受了全身皮质类固醇激素治疗。

In patients with ALT ≥3 times upper limit of normal (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients who were rechallenged with either KEYTRUDA (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT ≥3 times ULN was observed in 1 patient receiving KEYTRUDA, 16 patients receiving axitinib, and 24 patients receiving both.

ALT≥3倍正常上限（ULN）的患者（2-4级，n=116），ALT在94%中降至0-1级。在92例接受KEYTRUDA（n=3）或axitinib（n=34）作为单一药物或两者（n=55）再次攻击的患者中，1例接受KEYTRUDA治疗的患者ALT≥3倍ULN复发，16例接受axitinib治疗的患者和24例接受两者治疗的患者。

All patients with a recurrence of ALT ≥3 ULN subsequently recovered from the event..

所有ALT≥3 ULN复发的患者随后均从事件中恢复。。

Immune-Mediated Endocrinopathies

免疫介导的内分泌病

Adrenal Insufficiency

肾上腺皮质功能不全

KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.3%) reactions.

KEYTRUDA可引起原发性或继发性肾上腺功能不全。对于2级或更高级别，开始对症治疗，包括临床指示的激素替代。根据严重程度扣留KEYTRUDA。接受KEYTRUDA治疗的患者中有0.8%（22/2799）发生肾上腺功能不全，包括4级（<0.1%），3级（0.3%）和2级（0.3%）反应。

Systemic corticosteroids were required in 77% (17/22) of patients; of these, the majority remained on systemic corticosteroids. Adrenal insufficiency led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.3% (8) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement..

77%（17/22）的患者需要全身皮质类固醇；其中，大多数仍然服用全身性皮质类固醇。肾上腺功能不全导致0.1%（1）的患者永久停用KEYTRUDA，0.3%（8）的患者停用KEYTRUDA。症状改善后，所有被扣留的患者都重新启动了KEYTRUDA。。

Hypophysitis

垂体炎

KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue KEYTRUDA depending on severity.

KEYTRUDA可引起免疫介导的垂体炎。垂体炎可出现与肿块效应相关的急性症状，例如头痛，畏光或视野缺陷。。如图所示开始激素替代。根据严重程度扣留或永久停用KEYTRUDA。

Hypophysitis occurred in 0.6% (17/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.2%) reactions. Systemic corticosteroids were required in 94% (16/17) of patients; of these, the majority remained on systemic corticosteroids. Hypophysitis led to permanent discontinuation of KEYTRUDA in 0.1% (4) and withholding in 0.3% (7) of patients.

接受KEYTRUDA治疗的患者中有0.6%（17/2799）发生垂体炎，包括4级（<0.1%），3级（0.3%）和2级（0.2%）反应。94%（16/17）的患者需要全身皮质类固醇；其中，大多数仍然服用全身性皮质类固醇。垂体炎导致0.1%（4）的患者永久停止使用KEYTRUDA，0.3%（7）的患者停止使用KEYTRUDA。

All patients who were withheld reinitiated KEYTRUDA after symptom improvement..

症状改善后，所有被扣留的患者都重新启动了KEYTRUDA。。

Thyroid Disorders

甲状腺疾病

KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue KEYTRUDA depending on severity.

KEYTRUDA可引起免疫介导的甲状腺疾病。甲状腺炎可伴有或不伴有内分泌病。甲状腺功能减退症可继发于甲状腺功能亢进症。根据临床指示，开始甲状腺功能减退症的激素替代或甲状腺功能亢进症的医疗管理。根据严重程度扣留或永久停用KEYTRUDA。

Thyroiditis occurred in 0.6% (16/2799) of patients receiving KEYTRUDA, including Grade 2 (0.3%). None discontinued, but KEYTRUDA was withheld in <0.1% (1) of patients..

接受KEYTRUDA治疗的患者中有0.6%（16/2799）发生甲状腺炎，包括2级（0.3%）。没有停药，但KEYTRUDA在0.1%（1）的患者中被扣留。。

Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent discontinuation of KEYTRUDA in <0.1% (2) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

接受KEYTRUDA治疗的患者中有3.4%（96/2799）发生甲状腺功能亢进，包括3级（0.1%）和2级（0.8%）。它导致<0.1%（2）的患者永久停止使用KEYTRUDA，0.3%（7）的患者停止使用KEYTRUDA。症状改善后，所有被扣留的患者都重新启动了KEYTRUDA。

Hypothyroidism occurred in 8% (237/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (6.2%). It led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.5% (14) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. The majority of patients with hypothyroidism required long-term thyroid hormone replacement.

接受KEYTRUDA治疗的患者中有8%（237/2799）发生甲状腺功能减退，包括3级（0.1%）和2级（6.2%）。它导致<0.1%（1）的患者永久停止使用KEYTRUDA，0.5%（14）的患者停止使用KEYTRUDA。症状改善后，所有被扣留的患者都重新启动了KEYTRUDA。大多数甲状腺功能减退症患者需要长期更换甲状腺激素。

The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC, occurring in 16% of patients receiving KEYTRUDA as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in 389 adult patients with cHL (17%) receiving KEYTRUDA as a single agent, including Grade 1 (6.2%) and Grade 2 (10.8%) hypothyroidism.

1185例HNSCC患者中新发或恶化的甲状腺功能减退症发生率较高，其中16%的患者接受KEYTRUDA作为单一药物或与铂和FU联合治疗，包括3级（0.3%）甲状腺功能减退症。389名接受KEYTRUDA作为单一药物治疗的成年cHL患者（17%）新发或恶化的甲状腺功能减退症发生率较高，包括1级（6.2%）和2级（10.8%）甲状腺功能减退症。

The incidence of new or worsening hyperthyroidism was higher in 580 patients with resected NSCLC, occurring in 11% of patients receiving KEYTRUDA as a single agent as adjuvant treatment, including Grade 3 (0.2%) hyperthyroidism. The incidence of new or worsening hypothyroidism was higher in 580 patients with resected NSCLC, occurring in 22% of patients receiving KEYTRUDA as a single agent as adjuvant treatment (KEYNOTE-091), including Grade 3 (0.3%) hypothyroidism..

580例切除的非小细胞肺癌患者中，新发或恶化的甲状腺功能亢进发生率较高，其中11%的患者接受KEYTRUDA作为单一药物作为辅助治疗，包括3级（0.2%）甲状腺功能亢进。580例切除的NSCLC患者中新发或恶化的甲状腺功能减退症发生率较高，22%的患者接受KEYTRUDA作为单一药物作为辅助治疗（KEYNOTE-091），包括3级（0.3%）甲状腺功能减退症。。

Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic Ketoacidosis

1型糖尿病（DM），可伴有糖尿病酮症酸中毒

Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA depending on severity. Type 1 DM occurred in 0.2% (6/2799) of patients receiving KEYTRUDA. It led to permanent discontinuation in <0.1% (1) and withholding of KEYTRUDA in <0.1% (1) of patients.

监测患者的高血糖或其他糖尿病体征和症状。根据临床指示开始胰岛素治疗。根据严重程度扣留KEYTRUDA。接受KEYTRUDA治疗的患者中有0.2%（6/2799）发生1型糖尿病。它导致<0.1%（1）的患者永久停药，而<0.1%（1）的患者停止使用KEYTRUDA。

All patients who were withheld reinitiated KEYTRUDA after symptom improvement..

症状改善后，所有被扣留的患者都重新启动了KEYTRUDA。。

Immune-Mediated Nephritis With Renal Dysfunction

免疫介导性肾炎伴肾功能不全

KEYTRUDA can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.1%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 89% (8/9) of patients. Nephritis led to permanent discontinuation of KEYTRUDA in 0.1% (3) and withholding in 0.1% (3) of patients.

KEYTRUDA可引起免疫介导的肾炎。接受KEYTRUDA治疗的患者中有0.3%（9/2799）发生免疫介导的肾炎，包括4级（<0.1%），3级（0.1%）和2级（0.1%）反应。89%（8/9）的患者需要全身皮质类固醇。肾炎导致0.1%（3）的患者永久停止使用KEYTRUDA，0.1%（3）的患者停止使用KEYTRUDA。

All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Nephritis resolved in 56% of the 9 patients..

；其中，没有人复发。9例患者中有56%的肾炎消退。。

Immune-Mediated Dermatologic Adverse Reactions

免疫介导的皮肤病不良反应

KEYTRUDA can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with anti– PD-1/PD-L1 treatments. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes.

KEYTRUDA可引起免疫介导的皮疹或皮炎。抗PD-1/PD-L1治疗发生了剥脱性皮炎，包括史蒂文斯-约翰逊综合征，伴有嗜酸性粒细胞增多和全身症状的药疹以及中毒性表皮坏死松解症。局部润肤剂和/或局部皮质类固醇可能足以治疗轻度至中度非化脓性皮疹。

Withhold or permanently discontinue KEYTRUDA depending on severity. Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 40% (15/38) of patients. These reactions led to permanent discontinuation in 0.1% (2) and withholding of KEYTRUDA in 0.6% (16) of patients.

根据严重程度扣留或永久停用KEYTRUDA。接受KEYTRUDA治疗的患者中有1.4%（38/2799）发生免疫介导的皮肤病不良反应，包括3级（1%）和2级（0.1%）反应。40%（15/38）的患者需要全身皮质类固醇。。

All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 6% had recurrence. The reactions resolved in 79% of the 38 patients..

；其中6%复发。38名患者中有79%的反应得到了缓解。。

Other Immune-Mediated Adverse Reactions

其他免疫介导的不良反应

The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received KEYTRUDA or were reported with the use of other anti–PD-1/PD-L1 treatments. Severe or fatal cases have been reported for some of these adverse reactions.

在接受KEYTRUDA或报告使用其他抗PD-1/PD-L1治疗的患者中，以下临床上显着的免疫介导的不良反应发生率<1%（除非另有说明）。据报道，其中一些不良反应有严重或致命的病例。

Cardiac/Vascular: Myocarditis, pericarditis, vasculitis; Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy; Ocular: Uveitis, iritis and other ocular inflammatory toxicities can occur.

心脏/血管：心肌炎，心包炎，血管炎；神经系统：脑膜炎，脑炎，脊髓炎和脱髓鞘，肌无力综合征/重症肌无力（包括恶化），格林-巴利综合征，神经麻痹，自身免疫性神经病；眼部：可能发生葡萄膜炎，虹膜炎和其他眼部炎症毒性。

Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; Gastrointestinal: Pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis (and associated sequelae, including renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, other transplant (including corneal graft) rejection..

有些病例可能与视网膜脱离有关。可能会出现各种程度的视力障碍，包括失明。如果葡萄膜炎与其他免疫介导的不良反应相结合，请考虑Vogt-Koyanagi-Harada样综合征，因为这可能需要用全身类固醇治疗以降低永久性视力丧失的风险；胃肠道：胰腺炎，包括血清淀粉酶和脂肪酶水平升高，胃炎，十二指肠炎；肌肉骨骼和结缔组织：肌炎/多发性肌炎，横纹肌溶解症（及相关后遗症，包括肾衰竭），关节炎（1.5%），风湿性多肌痛；内分泌：甲状旁腺功能减退；血液学/免疫：溶血性贫血、再生障碍性贫血、吞噬性淋巴组织细胞增多症、全身炎症反应综合征、组织细胞坏死性淋巴结炎（菊池淋巴结炎）、结节病、免疫性血小板减少性紫癜、实体器官移植排斥反应、其他移植（包括角膜移植）排斥反应。。

Infusion-Related Reactions

输液相关反应

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% of 2799 patients receiving KEYTRUDA. Monitor for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion for Grade 1 or Grade 2 reactions.

KEYTRUDA可引起严重或危及生命的输液相关反应，包括超敏反应和过敏反应，据报道，在接受KEYTRUDA的2799名患者中，有0.2%的患者发生了这种反应。。中断或减慢1级或2级反应的输注速度。

For Grade 3 or Grade 4 reactions, stop infusion and permanently discontinue KEYTRUDA..

对于3级或4级反应，停止输注并永久停止KEYTRUDA。。

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

异基因造血干细胞移植（HSCT）的并发症

Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after anti–PD-1/PD-L1 treatments. Transplant- related complications include hyperacute graft-versus-host disease (GVHD), acute and chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause).

在抗PD-1/PD-L1治疗之前或之后接受同种异体HSCT的患者可能会发生致命和其他严重并发症。与移植相关的并发症包括超急性移植物抗宿主病（GVHD），急性和慢性GVHD，降低强度调理后的肝静脉闭塞性疾病以及需要类固醇的发热综合征（没有确定的感染原因）。

These complications may occur despite intervening therapy between anti–PD-1/PD-L1 treatments and allogeneic HSCT. Follow patients closely for evidence of these complications and intervene promptly. Consider the benefit vs risks of using anti–PD-1/PD-L1 treatments prior to or after an allogeneic HSCT..

尽管在抗PD-1/PD-L1治疗和同种异体HSCT之间进行了干预治疗，但仍可能发生这些并发症。。考虑在同种异体HSCT之前或之后使用抗PD-1/PD-L1治疗的益处与风险。。

Increased Mortality in Patients With Multiple Myeloma

多发性骨髓瘤患者死亡率增加

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with an anti–PD-1/PD-L1 treatment in this combination is not recommended outside of controlled trials.

在多发性骨髓瘤患者的试验中，在沙利度胺类似物加地塞米松中加入KEYTRUDA导致死亡率增加。。

Embryofetal Toxicity

胚胎胎儿毒性

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose..

根据其作用机制，KEYTRUDA给孕妇服用时会对胎儿造成伤害。向女性告知这种潜在风险。对于具有生殖潜力的女性，在开始使用KEYTRUDA之前验证妊娠状况，并建议他们在治疗期间和最后一次服用后4个月内使用有效的避孕措施。。

Adverse Reactions

不良反应

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%).

在KEYNOTE-006中，555例晚期黑色素瘤患者中有9%因不良反应而停用KEYTRUDA；导致一名以上患者永久停药的不良反应为结肠炎（1.4%），自身免疫性肝炎（0.7%），过敏反应（0.4%），多发性神经病（0.4%）和心力衰竭（0.4%）。

The most common adverse reactions (≥20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%)..

KEYTRUDA最常见的不良反应（≥20%）是疲劳（28%），腹泻（26%），皮疹（24%）和恶心（21%）。。

In KEYNOTE-054, when KEYTRUDA was administered as a single agent to patients with stage III melanoma, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (≥1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA.

在KEYNOTE-054中，当KEYTRUDA作为单一药物给予III期黑色素瘤患者时，509名患者中有14%因不良反应而永久停用KEYTRUDA；最常见（≥1%）的是肺炎（1.4%），结肠炎（1.2%）和腹泻（1%）。接受KEYTRUDA治疗的患者中有25%发生严重不良反应。

The most common adverse reaction (≥20%) with KEYTRUDA was diarrhea (28%). In KEYNOTE-716, when KEYTRUDA was administered as a single agent to patients with stage IIB or IIC melanoma, adverse reactions occurring in patients with stage IIB or IIC melanoma were similar to those occurring in 1011 patients with stage III melanoma from KEYNOTE-054..

KEYTRUDA最常见的不良反应（≥20%）是腹泻（28%）。在KEYNOTE-716中，当KEYTRUDA作为单一药物用于IIB或IIC期黑色素瘤患者时，IIB或IIC期黑色素瘤患者发生的不良反应与KEYNOTE-054中1011例III期黑色素瘤患者发生的不良反应相似。。

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%).

。导致KEYTRUDA永久停药的最常见不良反应是肺炎（3%）和急性肾损伤（2%）。

The most common adverse reactions (≥20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%)..

KEYTRUDA最常见的不良反应（≥20%）是恶心（56%），疲劳（56%），便秘（35%），腹泻（31%），食欲下降（28%），皮疹（25%），呕吐（24%），咳嗽（21%），呼吸困难（21%）和发热（20%）。。

In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection.

在KEYNOTE-407中，当KEYTRUDA与卡铂和紫杉醇或紫杉醇蛋白结合在转移性鳞状NSCLC中时，101名患者中有15%因不良反应而停用KEYTRUDA。至少2%的患者报告的最常见的严重不良反应是发热性中性粒细胞减少症，肺炎和尿路感染。

Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407..

KEYNOTE-407中观察到的不良反应与KEYNOTE-189中观察到的相似，除了在KEYNOTE-407中观察到的脱发（47%比36%）和周围神经病变（31%比25%）的发生率增加相比，KEYNOTE-407中的安慰剂和化疗组。。

In KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in 19% of 636 patients with advanced NSCLC; the most common were pneumonitis (3%), death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%).

在KEYNOTE-042中，636例晚期非小细胞肺癌患者中有19%因不良反应而停用KEYTRUDA；最常见的是肺炎（3%），不明原因死亡（1.6%）和肺炎（1.4%）。至少2%的患者报告的最常见的严重不良反应是肺炎（7%），肺炎（3.9%），肺栓塞（2.4%）和胸腔积液（2.2%）。

The most common adverse reaction (≥20%) was fatigue (25%)..

最常见的不良反应（≥20%）是疲劳（25%）。。

In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis (1.8%). The most common adverse reactions (≥20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

在KEYNOTE-010中，682例转移性非小细胞肺癌患者中有8%因不良反应停止了KEYTRUDA单药治疗；最常见的是肺炎（1.8%）。最常见的不良反应（≥20%）是食欲下降（25%），疲劳（25%），呼吸困难（23%）和恶心（20%）。

In KEYNOTE-671, adverse reactions occurring in patients with resectable NSCLC receiving KEYTRUDA in combination with platinum-containing chemotherapy, given as neoadjuvant treatment and continued as single-agent adjuvant treatment, were generally similar to those occurring in patients in other clinical trials across tumor types receiving KEYTRUDA in combination with chemotherapy..

在KEYNOTE-671中，接受KEYTRUDA联合含铂化疗（作为新辅助治疗并继续作为单药辅助治疗）的可切除NSCLC患者发生的不良反应通常与接受KEYTRUDA联合化疗的其他肿瘤类型临床试验患者发生的不良反应相似。。

The most common adverse reactions (reported in ≥20%) in patients receiving KEYTRUDA in combination with chemotherapy were fatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, pyrexia, alopecia, peripheral neuropathy, mucosal inflammation, stomatitis, headache, weight loss, abdominal pain, arthralgia, myalgia, insomnia, palmar- plantar erythrodysesthesia, urinary tract infection, and hypothyroidism..

接受KEYTRUDA联合化疗的患者最常见的不良反应（报告≥20%）是疲劳/乏力，恶心，便秘，腹泻，食欲下降，皮疹，呕吐，咳嗽，呼吸困难，发热，脱发，周围神经病变，粘膜炎，口腔炎，头痛，体重减轻，腹痛，关节痛，肌痛，失眠，掌底红细胞感觉异常，尿路感染和甲状腺功能减退。。

In the neoadjuvant phase of KEYNOTE-671, when KEYTRUDA was administered in combination with platinum-containing chemotherapy as neoadjuvant treatment, serious adverse reactions occurred in 34% of 396 patients. The most frequent (≥2%) serious adverse reactions were pneumonia (4.8%), venous thromboembolism (3.3%), and anemia (2%).

在KEYNOTE-671的新辅助治疗阶段，当KEYTRUDA联合含铂化疗作为新辅助治疗时，396例患者中有34%发生严重不良反应。最常见（≥2%）的严重不良反应是肺炎（4.8%），静脉血栓栓塞（3.3%）和贫血（2%）。

Fatal adverse reactions occurred in 1.3% of patients, including death due to unknown cause (0.8%), sepsis (0.3%), and immune-mediated lung disease (0.3%). Permanent discontinuation of any study drug due to an adverse reaction occurred in 18% of patients who received KEYTRUDA in combination with platinum-containing chemotherapy; the most frequent adverse reactions (≥1%) that led to permanent discontinuation of any study drug were acute kidney injury (1.8%), interstitial lung disease (1.8%), anemia (1.5%), neutropenia (1.5%), and pneumonia (1.3%)..

1.3%的患者发生致命的不良反应，包括不明原因死亡（0.8%），败血症（0.3%）和免疫介导的肺部疾病（0.3%）。18%接受KEYTRUDA联合含铂化疗的患者因不良反应而永久停用任何研究药物；导致任何研究药物永久停药的最常见不良反应（≥1%）是急性肾损伤（1.8%），间质性肺病（1.8%），贫血（1.5%），中性粒细胞减少症（1.5%）和肺炎（1.3%）。。

Of the KEYTRUDA-treated patients who received neoadjuvant treatment, 6% of 396 patients did not receive surgery due to adverse reactions. The most frequent (≥1%) adverse reaction that led to cancellation of surgery in the KEYTRUDA arm was interstitial lung disease (1%).

在接受新辅助治疗的KEYTRUDA治疗患者中，396名患者中有6%因不良反应未接受手术。导致KEYTRUDA组手术取消的最常见（≥1%）不良反应是间质性肺病（1%）。

In the adjuvant phase of KEYNOTE-671, when KEYTRUDA was administered as a single agent as adjuvant treatment, serious adverse reactions occurred in 14% of 290 patients. The most frequent serious adverse reaction was pneumonia (3.4%). One fatal adverse reaction of pulmonary hemorrhage occurred. Permanent discontinuation of KEYTRUDA due to an adverse reaction occurred in 12% of patients who received KEYTRUDA as a single agent, given as adjuvant treatment; the most frequent adverse reactions (≥1%) that led to permanent discontinuation of KEYTRUDA were diarrhea (1.7%), interstitial lung disease (1.4%), increased aspartate aminotransferase (1%), and musculoskeletal pain (1%)..

在KEYNOTE-671的辅助阶段，当KEYTRUDA作为单一药物作为辅助治疗时，290名患者中有14%发生了严重的不良反应。最常见的严重不良反应是肺炎（3.4%）。发生一例致命的肺出血不良反应。12%接受KEYTRUDA作为单一药物的患者因不良反应而永久停用KEYTRUDA，作为辅助治疗；导致KEYTRUDA永久停药的最常见不良反应（≥1%）是腹泻（1.7%），间质性肺病（1.4%），天冬氨酸转氨酶升高（1%）和肌肉骨骼疼痛（1%）。。

Adverse reactions observed in KEYNOTE-091 were generally similar to those occurring in other patients with NSCLC receiving KEYTRUDA as a single agent, with the exception of hypothyroidism (22%), hyperthyroidism (11%), and pneumonitis (7%). Two fatal adverse reactions of myocarditis occurred.

KEYNOTE-091中观察到的不良反应通常与接受KEYTRUDA作为单一药物的其他NSCLC患者发生的不良反应相似，但甲状腺功能减退症（22%），甲状腺功能亢进症（11%）和肺炎（7%）除外。发生了两次致命的心肌炎不良反应。

In KEYNOTE-048, KEYTRUDA monotherapy was discontinued due to adverse events in 12% of 300 patients with HNSCC; the most common adverse reactions leading to permanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The most common adverse reactions (≥20%) were fatigue (33%), constipation (20%), and rash (20%)..

在KEYNOTE-048中，300例HNSCC患者中有12%因不良事件停止了KEYTRUDA单药治疗；导致永久停药的最常见不良反应是败血症（1.7%）和肺炎（1.3%）。最常见的不良反应（≥20%）是疲劳（33%），便秘（20%）和皮疹（20%）。。

In KEYNOTE-048, when KEYTRUDA was administered in combination with platinum (cisplatin or carboplatin) and FU chemotherapy, KEYTRUDA was discontinued due to adverse reactions in 16% of 276 patients with HNSCC. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonia (2.5%), pneumonitis (1.8%), and septic shock (1.4%).

在KEYNOTE-048中，当KEYTRUDA与铂（顺铂或卡铂）和FU化疗联合使用时，276例HNSCC患者中有16%因不良反应而停用KEYTRUDA。导致KEYTRUDA永久停药的最常见不良反应是肺炎（2.5%），肺炎（1.8%）和感染性休克（1.4%）。

The most common adverse reactions (≥20%) were nausea (51%), fatigue (49%), constipation (37%), vomiting (32%), mucosal inflammation (31%), diarrhea (29%), decreased appetite (29%), stomatitis (26%), and cough (22%)..

最常见的不良反应（≥20%）是恶心（51%），疲劳（49%），便秘（37%），呕吐（32%），粘膜炎（31%），腹泻（29%），食欲下降（29%），口腔炎（26%）和咳嗽（22%）。。

In KEYNOTE-012, KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure.

在KEYNOTE-012中，192例HNSCC患者中有17%因不良反应而停用KEYTRUDA。45%的患者发生严重不良反应。至少2%的患者报告的最常见的严重不良反应是肺炎，呼吸困难，混乱状态，呕吐，胸腔积液和呼吸衰竭。

The most common adverse reactions (≥20%) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of facial edema and new or worsening hypothyroidism..

最常见的不良反应（≥20%）是疲劳，食欲下降和呼吸困难。HNSCC患者发生的不良反应通常与接受KEYTRUDA作为单一疗法的黑色素瘤或NSCLC患者发生的不良反应相似，除了面部水肿和新发或恶化的甲状腺功能减退症的发生率增加。。

In KEYNOTE-204, KEYTRUDA was discontinued due to adverse reactions in 14% of 148 patients with cHL. Serious adverse reactions occurred in 30% of patients receiving KEYTRUDA; those ≥1% were pneumonitis, pneumonia, pyrexia, myocarditis, acute kidney injury, febrile neutropenia, and sepsis. Three patients died from causes other than disease progression: 2 from complications after allogeneic HSCT and 1 from unknown cause.

在KEYNOTE-204中，148例cHL患者中有14%因不良反应而停用KEYTRUDA。接受KEYTRUDA治疗的患者中有30%发生严重不良反应；这些≥1%是肺炎，肺炎，发热，心肌炎，急性肾损伤，发热性中性粒细胞减少症和败血症。三名患者死于疾病进展以外的原因：2名死于同种异体HSCT后的并发症，1名死于不明原因。

The most common adverse reactions (≥20%) were upper respiratory tract infection (41%), musculoskeletal pain (32%), diarrhea (22%), and pyrexia, fatigue, rash, and cough (20% each)..

最常见的不良反应（≥20%）是上呼吸道感染（41%），肌肉骨骼疼痛（32%），腹泻（22%）和发热，疲劳，皮疹和咳嗽（各20%）。。

In KEYNOTE-087, KEYTRUDA was discontinued due to adverse reactions in 5% of 210 patients with cHL. Serious adverse reactions occurred in 16% of patients; those ≥1% were pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two patients died from causes other than disease progression: 1 from GVHD after subsequent allogeneic HSCT and 1 from septic shock.

在KEYNOTE-087中，210例cHL患者中有5%因不良反应而停用KEYTRUDA。16%的患者发生严重不良反应；这些≥1%是肺炎，肺炎，发热，呼吸困难，GVHD和带状疱疹。两名患者死于疾病进展以外的原因：1名死于随后的同种异体HSCT后的GVHD，1名死于感染性休克。

The most common adverse reactions (≥20%) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%)..

最常见的不良反应（≥20%）是疲劳（26%），发热（24%），咳嗽（24%），肌肉骨骼疼痛（21%），腹泻（20%）和皮疹（20%）。。

In KEYNOTE-170, KEYTRUDA was discontinued due to adverse reactions in 8% of 53 patients with PMBCL. Serious adverse reactions occurred in 26% of patients and included arrhythmia (4%), cardiac tamponade (2%), myocardial infarction (2%), pericardial effusion (2%), and pericarditis (2%). Six (11%) patients died within 30 days of start of treatment.

在KEYNOTE-170中，53例PMBCL患者中有8%因不良反应而停用KEYTRUDA。26%的患者发生严重不良反应，包括心律失常（4%），心脏压塞（2%），心肌梗塞（2%），心包积液（2%）和心包炎（2%）。六名（11%）患者在治疗开始后30天内死亡。

The most common adverse reactions (≥20%) were musculoskeletal pain (30%), upper respiratory tract infection and pyrexia (28% each), cough (26%), fatigue (23%), and dyspnea (21%)..

最常见的不良反应（≥20%）是肌肉骨骼疼痛（30%），上呼吸道感染和发热（各28%），咳嗽（26%），疲劳（23%）和呼吸困难（21%）。。

In KEYNOTE-A39, when KEYTRUDA was administered in combination with enfortumab vedotin to patients with locally advanced or metastatic urothelial cancer (n=440), fatal adverse reactions occurred in 3.9% of patients, including acute respiratory failure (0.7%), pneumonia (0.5%), and pneumonitis/ILD (0.2%).

在KEYNOTE-A39中，当KEYTRUDA与enfortumab vedotin联合用于局部晚期或转移性尿路上皮癌患者（n=440）时，3.9%的患者发生致命不良反应，包括急性呼吸衰竭（0.7%），肺炎（0.5%）和肺炎/ILD（0.2%）。

Serious adverse reactions occurred in 50% of patients receiving KEYTRUDA in combination with enfortumab vedotin; the serious adverse reactions in ≥2% of patients were rash (6%), acute kidney injury (5%), pneumonitis/ILD (4.5%), urinary tract infection (3.6%), diarrhea (3.2%), pneumonia (2.3%), pyrexia (2%), and hyperglycemia (2%).

接受KEYTRUDA联合enfortumab vedotin治疗的患者中有50%发生严重不良反应；≥2%的患者严重不良反应为皮疹（6%），急性肾损伤（5%），肺炎/ILD（4.5%），尿路感染（3.6%），腹泻（3.2%），肺炎（2.3%），发热（2%）和高血糖（2%）。

Permanent discontinuation of KEYTRUDA occurred in 27% of patients. The most common adverse reactions (≥2%) resulting in permanent discontinuation of KEYTRUDA were pneumonitis/ILD (4.8%) and rash (3.4%). The most common adverse reactions (≥20%) occurring in patients treated with KEYTRUDA in combination with enfortumab vedotin were rash (68%), peripheral neuropathy (67%), fatigue (51%), pruritus (41%), diarrhea (38%), alopecia (35%), weight loss (33%), decreased appetite (33%), nausea (26%), constipation (26%), dry eye (24%), dysgeusia (21%), and urinary tract infection (21%)..

27%的患者永久停用KEYTRUDA。导致KEYTRUDA永久停药的最常见不良反应（≥2%）是肺炎/ILD（4.8%）和皮疹（3.4%）。KEYTRUDA联合enfortumab vedotin治疗的患者最常见的不良反应（≥20%）是皮疹（68%），周围神经病变（67%），疲劳（51%），瘙痒（41%），腹泻（38%），脱发（35%），体重减轻（33%），食欲下降（33%），恶心（26%），便秘（26%），干眼症（24%），味觉障碍（21%）和尿路感染（21%）。。

In KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in 11% of 370 patients with locally advanced or metastatic urothelial carcinoma. Serious adverse reactions occurred in 42% of patients; those ≥2% were urinary tract infection, hematuria, acute kidney injury, pneumonia, and urosepsis.

在KEYNOTE-052中，370例局部晚期或转移性尿路上皮癌患者中有11%因不良反应而停用KEYTRUDA。42%的患者发生严重不良反应；这些≥2%是尿路感染，血尿，急性肾损伤，肺炎和尿脓毒症。

The most common adverse reactions (≥20%) were fatigue (38%), musculoskeletal pain (24%), decreased appetite (22%), constipation (21%), rash (21%), and diarrhea (20%)..

最常见的不良反应（≥20%）是疲劳（38%），肌肉骨骼疼痛（24%），食欲下降（22%），便秘（21%），皮疹（21%）和腹泻（20%）。。

In KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in 8% of 266 patients with locally advanced or metastatic urothelial carcinoma. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.9%). Serious adverse reactions occurred in 39% of KEYTRUDA-treated patients; those ≥2% were urinary tract infection, pneumonia, anemia, and pneumonitis.

在KEYNOTE-045中，在266例局部晚期或转移性尿路上皮癌患者中，有8%的患者因不良反应而停用了KEYTRUDA。导致KEYTRUDA永久停药的最常见不良反应是肺炎（1.9%）。39%的KEYTRUDA治疗患者发生严重不良反应；那些≥2%是尿路感染，肺炎，贫血和肺炎。

The most common adverse reactions (≥20%) in patients who received KEYTRUDA were fatigue (38%), musculoskeletal pain (32%), pruritus (23%), decreased appetite (21%), nausea (21%), and rash (20%)..

接受KEYTRUDA治疗的患者最常见的不良反应（≥20%）是疲劳（38%），肌肉骨骼疼痛（32%），瘙痒（23%），食欲下降（21%），恶心（21%）和皮疹（20%）。。

In KEYNOTE-057, KEYTRUDA was discontinued due to adverse reactions in 11% of 148 patients with high-risk NMIBC. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.4%). Serious adverse reactions occurred in 28% of patients; those ≥2% were pneumonia (3%), cardiac ischemia (2%), colitis (2%), pulmonary embolism (2%), sepsis (2%), and urinary tract infection (2%).

在KEYNOTE-057中，148例高危NMIBC患者中有11%因不良反应而停用KEYTRUDA。导致KEYTRUDA永久停药的最常见不良反应是肺炎（1.4%）。28%的患者发生严重不良反应；≥2%为肺炎（3%），心脏缺血（2%），结肠炎（2%），肺栓塞（2%），败血症（2%）和尿路感染（2%）。

The most common adverse reactions (≥20%) were fatigue (29%), diarrhea (24%), and rash (24%)..

最常见的不良反应（≥20%）是疲劳（29%），腹泻（24%）和皮疹（24%）。。

Adverse reactions occurring in patients with MSI-H or dMMR CRC were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

MSI-H或dMMR CRC患者发生的不良反应与接受KEYTRUDA作为单一疗法的黑色素瘤或NSCLC患者发生的不良反应相似。

In KEYNOTE-158 and KEYNOTE-164, adverse reactions occurring in patients with MSI-H or dMMR cancer were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.

在KEYNOTE-158和KEYNOTE-164中，MSI-H或dMMR癌症患者发生的不良反应与接受KEYTRUDA作为单一药物的其他实体瘤患者发生的不良反应相似。

In KEYNOTE-811, when KEYTRUDA was administered in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, KEYTRUDA was discontinued due to adverse reactions in 6% of 217 patients with locally advanced unresectable or metastatic HER2+ gastric or GEJ adenocarcinoma. The most common adverse reaction resulting in permanent discontinuation was pneumonitis (1.4%).

在KEYNOTE-811中，当KEYTRUDA与曲妥珠单抗，氟嘧啶和含铂化疗联合使用时，217例局部晚期不可切除或转移性HER2+胃腺癌或GEJ腺癌患者中有6%因不良反应而停用KEYTRUDA。导致永久停药的最常见不良反应是肺炎（1.4%）。

In the KEYTRUDA arm versus placebo, there was a difference of ≥5% incidence between patients treated with KEYTRUDA vs standard of care for diarrhea (53% vs 44%) and nausea (49% vs 44%)..

在KEYTRUDA组与安慰剂组中，使用KEYTRUDA治疗的患者与腹泻标准治疗（53%比44%）和恶心（49%比44%）的患者之间的发生率差异≥5%。。

In KEYNOTE-859, when KEYTRUDA was administered in combination with fluoropyrimidine- and platinum-containing chemotherapy, serious adverse reactions occurred in 45% of 785 patients. Serious adverse reactions in >2% of patients included pneumonia (4.1%), diarrhea (3.9%), hemorrhage (3.9%), and vomiting (2.4%).

在KEYNOTE-859中，当KEYTRUDA与含氟嘧啶和铂的化疗联合使用时，785名患者中有45%发生了严重的不良反应。>2%的患者出现严重不良反应，包括肺炎（4.1%），腹泻（3.9%），出血（3.9%）和呕吐（2.4%）。

Fatal adverse reactions occurred in 8% of patients who received KEYTRUDA including infection (2.3%) and thromboembolism (1.3%). KEYTRUDA was permanently discontinued due to adverse reactions in 15% of patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA (≥1%) were infections (1.8%) and diarrhea (1.0%).

接受KEYTRUDA治疗的患者中有8%发生致命不良反应，包括感染（2.3%）和血栓栓塞（1.3%）。由于15%的患者出现不良反应，KEYTRUDA永久停药。导致KEYTRUDA永久停药（≥1%）的最常见不良反应是感染（1.8%）和腹泻（1.0%）。

The most common adverse reactions (reported in ≥20%) in patients receiving KEYTRUDA in combination with chemotherapy were peripheral neuropathy (47%), nausea (46%), fatigue (40%), diarrhea (36%), vomiting (34%), decreased appetite (29%), abdominal pain (26%), palmar-plantar erythrodysesthesia syndrome (25%), constipation (22%), and weight loss (20%)..

接受KEYTRUDA联合化疗的患者最常见的不良反应（报告≥20%）是周围神经病变（47%），恶心（46%），疲劳（40%），腹泻（36%），呕吐（34%），食欲下降（29%），腹痛（26%），掌底红细胞感觉异常综合征（25%），便秘（22%）和体重减轻（20%）。。

In KEYNOTE-590, when KEYTRUDA was administered with cisplatin and fluorouracil to patients with metastatic or locally advanced esophageal or GEJ (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma who were not candidates for surgical resection or definitive chemoradiation, KEYTRUDA was discontinued due to adverse reactions in 15% of 370 patients.

在KEYNOTE-590中，当KEYTRUDA与顺铂和氟尿嘧啶联合应用于转移性或局部晚期食管癌或GEJ（震中高于GEJ 1至5厘米的肿瘤）患者时，这些患者不适合手术切除或确定性放化疗，KEYTRUDA因370例患者中15%的不良反应而停药。

The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA (≥1%) were pneumonitis (1.6%), acute kidney injury (1.1%), and pneumonia (1.1%). The most common adverse reactions (≥20%) with KEYTRUDA in combination with chemotherapy were nausea (67%), fatigue (57%), decreased appetite (44%), constipation (40%), diarrhea (36%), vomiting (34%), stomatitis (27%), and weight loss (24%)..

导致KEYTRUDA永久停药（≥1%）的最常见不良反应是肺炎（1.6%），急性肾损伤（1.1%）和肺炎（1.1%）。KEYTRUDA联合化疗最常见的不良反应（≥20%）是恶心（67%），疲劳（57%），食欲下降（44%），便秘（40%），腹泻（36%），呕吐（34%），口腔炎（27%）和体重减轻（24%）。。

Adverse reactions occurring in patients with esophageal cancer who received KEYTRUDA as a monotherapy were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

接受KEYTRUDA作为单一疗法的食管癌患者发生的不良反应与接受KEYTRUDA作为单一疗法的黑色素瘤或NSCLC患者发生的不良反应相似。

In KEYNOTE-A18, when KEYTRUDA was administered with CRT (cisplatin plus external beam radiation therapy [EBRT] followed by brachytherapy [BT]) to patients with FIGO 2014 Stage III-IVA cervical cancer, fatal adverse reactions occurred in 1.4% of 292 patients, including 1 case each (0.3%) of large intestinal perforation, urosepsis, sepsis, and vaginal hemorrhage.

。

Serious adverse reactions occurred in 30% of patients; those ≥1% included urinary tract infection (2.7%), urosepsis (1.4%), and sepsis (1%). KEYTRUDA was discontinued for adverse reactions in 7% of patients. The most common adverse reaction (≥1%) resulting in permanent discontinuation was diarrhea (1%).

30%的患者发生严重不良反应；那些≥1%的患者包括尿路感染（2.7%），尿脓毒症（1.4%）和脓毒症（1%）。KEYTRUDA因7%的患者出现不良反应而停药。导致永久停药的最常见不良反应（≥1%）是腹泻（1%）。

For patients treated with KEYTRUDA in combination with CRT, the most common adverse reactions (≥10%) were nausea (56%), diarrhea (50%), vomiting (33%), urinary tract infection (32%), fatigue (26%), hypothyroidism (20%), constipation (18%), decreased appetite and weight loss (17% each), abdominal pain and pyrexia (12% each), hyperthyroidism, dysuria, rash (11% each), and pelvic pain (10%)..

对于使用KEYTRUDA联合CRT治疗的患者，最常见的不良反应（≥10%）是恶心（56%），腹泻（50%），呕吐（33%），尿路感染（32%），疲劳（26%），甲状腺功能减退（20%），便秘（18%），食欲下降和体重减轻（各17%），腹痛和发热（各12%），甲状腺功能亢进，排尿困难，皮疹（各11%）和骨盆疼痛（10%）。。

In KEYNOTE-826, when KEYTRUDA was administered in combination with paclitaxel and cisplatin or paclitaxel and carboplatin, with or without bevacizumab (n=307), to patients with persistent, recurrent, or first-line metastatic cervical cancer regardless of tumor PD-L1 expression who had not been treated with chemotherapy except when used concurrently as a radio- sensitizing agent, fatal adverse reactions occurred in 4.6% of patients, including 3 cases of hemorrhage, 2 cases each of sepsis and due to unknown causes, and 1 case each of acute myocardial infarction, autoimmune encephalitis, cardiac arrest, cerebrovascular accident, femur fracture with perioperative pulmonary embolus, intestinal perforation, and pelvic infection.

在KEYNOTE-826中，当KEYTRUDA与紫杉醇和顺铂或紫杉醇和卡铂联合使用，有或没有贝伐单抗（n=307）时，对于持续性，复发性或一线转移性宫颈癌患者，无论肿瘤PD-L1表达如何，除非同时用作放射增敏剂，否则未接受化疗，4.6%的患者发生致命不良反应，包括3例出血，2例败血症和原因不明，以及1例急性心肌梗死，自身免疫性脑炎，心脏骤停，脑血管意外，股骨骨折伴围手术期肺栓塞，肠穿孔和盆腔感染。

Serious adverse reactions occurred in 50% of patients receiving KEYTRUDA in combination with chemotherapy with or without bevacizumab; those ≥3% were febrile neutropenia (6.8%), urinary tract infection (5.2%), anemia (4.6%), and acute kidney injury and sepsis (3.3% each)..

接受KEYTRUDA联合化疗或不联合贝伐单抗治疗的患者中有50%发生严重不良反应；≥3%为发热性中性粒细胞减少症（6.8%），尿路感染（5.2%），贫血（4.6%），急性肾损伤和败血症（各3.3%）。。

KEYTRUDA was discontinued in 15% of patients due to adverse reactions. The most common adverse reaction resulting in permanent discontinuation (≥1%) was colitis (1%).

。导致永久停药（≥1%）的最常见不良反应是结肠炎（1%）。

For patients treated with KEYTRUDA, chemotherapy, and bevacizumab (n=196), the most common adverse reactions (≥20%) were peripheral neuropathy (62%), alopecia (58%), anemia (55%), fatigue/asthenia (53%), nausea and neutropenia (41% each), diarrhea (39%), hypertension and thrombocytopenia (35% each), constipation and arthralgia (31% each), vomiting (30%), urinary tract infection (27%), rash (26%), leukopenia (24%), hypothyroidism (22%), and decreased appetite (21%)..

对于接受KEYTRUDA，化疗和贝伐单抗治疗的患者（n=196），最常见的不良反应（≥20%）是周围神经病变（62%），脱发（58%），贫血（55%），疲劳/虚弱（53%），恶心和中性粒细胞减少症（各41%），腹泻（39%），高血压和血小板减少症（各35%），便秘和关节痛（各31%），呕吐（30%），尿路感染（27%），皮疹（26%），白细胞减少症（24%），甲状腺功能减退症（22%）和食欲下降（21%）。。

For patients treated with KEYTRUDA in combination with chemotherapy with or without bevacizumab, the most common adverse reactions (≥20%) were peripheral neuropathy (58%), alopecia (56%), fatigue (47%), nausea (40%), diarrhea (36%), constipation (28%), arthralgia (27%), vomiting (26%), hypertension and urinary tract infection (24% each), and rash (22%)..

对于使用KEYTRUDA联合化疗联合或不联合贝伐单抗治疗的患者，最常见的不良反应（≥20%）是周围神经病变（58%），脱发（56%），疲劳（47%），恶心（40%），腹泻（36%），便秘（28%），关节痛（27%），呕吐（26%），高血压和尿路感染（各24%）和皮疹（22%）。。

In KEYNOTE-158, KEYTRUDA was discontinued due to adverse reactions in 8% of 98 patients with previously treated recurrent or metastatic cervical cancer. Serious adverse reactions occurred in 39% of patients receiving KEYTRUDA; the most frequent included anemia (7%), fistula, hemorrhage, and infections [except urinary tract infections] (4.1% each).

在KEYNOTE-158中，98例先前接受过复发或转移性宫颈癌治疗的患者中有8%因不良反应而停用了KEYTRUDA。接受KEYTRUDA治疗的患者中有39%发生严重不良反应；最常见的包括贫血（7%），瘘管，出血和感染[尿路感染除外]（各4.1%）。

The most common adverse reactions (≥20%) were fatigue (43%), musculoskeletal pain (27%), diarrhea (23%), pain and abdominal pain (22% each), and decreased appetite (21%)..

最常见的不良反应（≥20%）是疲劳（43%），肌肉骨骼疼痛（27%），腹泻（23%），疼痛和腹痛（各22%）和食欲下降（21%）。。

In KEYNOTE-394, KEYTRUDA was discontinued due to adverse reactions in 13% of 299 patients with previously treated hepatocellular carcinoma. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was ascites (2.3%). The most common adverse reactions in patients receiving KEYTRUDA (≥10%) were pyrexia (18%), rash (18%), diarrhea (16%), decreased appetite (15%), pruritis (12%), upper respiratory tract infection (11%), cough (11%), and hypothyroidism (10%)..

在KEYNOTE-394中，在299例先前接受治疗的肝细胞癌患者中，有13%的患者因不良反应而停用了KEYTRUDA。导致KEYTRUDA永久停药的最常见不良反应是腹水（2.3%）。接受KEYTRUDA（≥10%）治疗的患者最常见的不良反应是发热（18%），皮疹（18%），腹泻（16%），食欲下降（15%），瘙痒症（12%），上呼吸道感染（11%），咳嗽（11%）和甲状腺功能减退（10%）。。

In KEYNOTE-966, when KEYTRUDA was administered in combination with gemcitabine and cisplatin, KEYTRUDA was discontinued for adverse reactions in 15% of 529 patients with locally advanced unresectable or metastatic biliary tract cancer. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA (≥1%) was pneumonitis (1.3%).

在KEYNOTE-966中，当KEYTRUDA与吉西他滨和顺铂联合使用时，529例局部晚期不可切除或转移性胆道癌患者中有15%因不良反应而停用KEYTRUDA。导致KEYTRUDA永久停药（≥1%）的最常见不良反应是肺炎（1.3%）。

Adverse reactions leading to the interruption of KEYTRUDA occurred in 55% of patients. The most common adverse reactions or laboratory abnormalities leading to interruption of KEYTRUDA (≥2%) were decreased neutrophil count (18%), decreased platelet count (10%), anemia (6%), decreased white blood cell count (4%), pyrexia (3.8%), fatigue (3.0%), cholangitis (2.8%), increased ALT (2.6%), increased AST (2.5%), and biliary obstruction (2.3%)..

55%的患者发生了导致KEYTRUDA中断的不良反应。导致KEYTRUDA中断（≥2%）的最常见的不良反应或实验室异常是中性粒细胞计数减少（18%），血小板计数减少（10%），贫血（6%），白细胞计数减少（4%），发热（3.8%），疲劳（3.0%），胆管炎（2.8%），ALT升高（2.6%），AST升高（2.5%）和胆道梗阻（2.3%）。。

In KEYNOTE-017 and KEYNOTE-913, adverse reactions occurring in patients with MCC (n=105) were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a single agent.

。

In KEYNOTE-426, when KEYTRUDA was administered in combination with axitinib, fatal adverse reactions occurred in 3.3% of 429 patients. Serious adverse reactions occurred in 40% of patients, the most frequent (≥1%) were hepatotoxicity (7%), diarrhea (4.2%), acute kidney injury (2.3%), dehydration (1%), and pneumonitis (1%).

在KEYNOTE-426中，当KEYTRUDA与阿西替尼联合使用时，429名患者中有3.3%发生致命的不良反应。40%的患者发生严重不良反应，最常见（≥1%）的是肝毒性（7%），腹泻（4.2%），急性肾损伤（2.3%），脱水（1%）和肺炎（1%）。

Permanent discontinuation due to an adverse reaction occurred in 31% of patients; KEYTRUDA only (13%), axitinib only (13%), and the combination (8%); the most common were hepatotoxicity (13%), diarrhea/colitis (1.9%), acute kidney injury (1.6%), and cerebrovascular accident (1.2%). The most common adverse reactions (≥20%) were diarrhea (56%), fatigue/asthenia (52%), hypertension (48%), hepatotoxicity (39%), hypothyroidism (35%), decreased appetite (30%), palmar-plantar erythrodysesthesia (28%), nausea (28%), stomatitis/mucosal inflammation (27%), dysphonia (25%), rash (25%), cough (21%), and constipation (21%)..

31%的患者因不良反应而永久停药；仅KEYTRUDA（13%），仅axitinib（13%）和组合（8%）；最常见的是肝毒性（13%），腹泻/结肠炎（1.9%），急性肾损伤（1.6%）和脑血管意外（1.2%）。最常见的不良反应（≥20%）是腹泻（56%），疲劳/虚弱（52%），高血压（48%），肝毒性（39%），甲状腺功能减退（35%），食欲下降（30%），掌底红细胞感觉异常（28%），恶心（28%），口腔炎/粘膜炎（27%），发音困难（25%），皮疹（25%），咳嗽（21%）和便秘（21%）。。

In KEYNOTE-581, when KEYTRUDA was administered in combination with LENVIMA to patients with advanced renal cell carcinoma (n=352), fatal adverse reactions occurred in 4.3% of patients. Serious adverse reactions occurred in 51% of patients; the most common (≥2%) were hemorrhagic events (5%), diarrhea (4%), hypertension, myocardial infarction, pneumonitis, and vomiting (3% each), acute kidney injury, adrenal insufficiency, dyspnea, and pneumonia (2% each)..

在KEYNOTE-581中，当KEYTRUDA与LENVIMA联合用于晚期肾细胞癌患者（n=352）时，4.3%的患者发生致命的不良反应。51%的患者发生严重不良反应；最常见的（≥2%）是出血事件（5%），腹泻（4%），高血压，心肌梗塞，肺炎和呕吐（各3%），急性肾损伤，肾上腺功能不全，呼吸困难和肺炎（各2%）。。

Permanent discontinuation of KEYTRUDA, LENVIMA, or both due to an adverse reaction occurred in 37% of patients; 29% KEYTRUDA only, 26% LENVIMA only, and 13% both. The most common adverse reaction (≥2%) resulting in permanent discontinuation of KEYTRUDA, LENVIMA, or the combination were pneumonitis, myocardial infarction, hepatotoxicity, acute kidney injury, rash (3% each), and diarrhea (2%)..

37%的患者因不良反应而永久停用KEYTRUDA，LENVIMA或两者；仅29%的KEYTRUDA，26%的LENVIMA，以及13%的两者。导致KEYTRUDA，LENVIMA或其组合永久停药的最常见不良反应（≥2%）是肺炎，心肌梗塞，肝毒性，急性肾损伤，皮疹（各3%）和腹泻（2%）。。

The most common adverse reactions (≥20%) observed with KEYTRUDA in combination with LENVIMA were fatigue (63%), diarrhea (62%), musculoskeletal disorders (58%), hypothyroidism (57%), hypertension (56%), stomatitis (43%), decreased appetite (41%), rash (37%), nausea (36%), weight loss, dysphonia and proteinuria (30% each), palmar-plantar erythrodysesthesia syndrome (29%), abdominal pain and hemorrhagic events (27% each), vomiting (26%), constipation and hepatotoxicity (25% each), headache (23%), and acute kidney injury (21%)..

KEYTRUDA联合LENVIMA观察到的最常见的不良反应（≥20%）是疲劳（63%），腹泻（62%），肌肉骨骼疾病（58%），甲状腺功能减退（57%），高血压（56%），口腔炎（43%），食欲下降（41%），皮疹（37%），恶心（36%），体重减轻，发音困难和蛋白尿（各30%），掌底红细胞感觉异常综合征（29%），腹痛和出血事件（各27%），呕吐（26%），便秘和肝毒性（各25%），头痛（23%）和急性肾损伤（21%）。。

In KEYNOTE-564, when KEYTRUDA was administered as a single agent for the adjuvant treatment of renal cell carcinoma, serious adverse reactions occurred in 20% of patients receiving KEYTRUDA; the serious adverse reactions (≥1%) were acute kidney injury, adrenal insufficiency, pneumonia, colitis, and diabetic ketoacidosis (1% each).

在KEYNOTE-564中，当KEYTRUDA作为单一药物用于肾细胞癌的辅助治疗时，接受KEYTRUDA的患者中有20%发生严重不良反应；严重不良反应（≥1%）为急性肾损伤，肾上腺功能不全，肺炎，结肠炎和糖尿病酮症酸中毒（各1%）。

Fatal adverse reactions occurred in 0.2% including 1 case of pneumonia. Discontinuation of KEYTRUDA due to adverse reactions occurred in 21% of 488 patients; the most common (≥1%) were increased ALT (1.6%), colitis (1%), and adrenal insufficiency (1%). The most common adverse reactions (≥20%) were musculoskeletal pain (41%), fatigue (40%), rash (30%), diarrhea (27%), pruritus (23%), and hypothyroidism (21%)..

致命不良反应发生率为0.2%，包括1例肺炎。488例患者中有21%因不良反应停用KEYTRUDA；最常见的（≥1%）是ALT升高（1.6%），结肠炎（1%）和肾上腺功能不全（1%）。最常见的不良反应（≥20%）是肌肉骨骼疼痛（41%），疲劳（40%），皮疹（30%），腹泻（27%），瘙痒（23%）和甲状腺功能减退（21%）。。

In KEYNOTE-868, when KEYTRUDA was administered in combination with chemotherapy (paclitaxel and carboplatin) to patients with advanced or recurrent endometrial carcinoma (n=382), serious adverse reactions occurred in 35% of patients receiving KEYTRUDA in combination with chemotherapy, compared to 19% of patients receiving placebo in combination with chemotherapy (n=377).

在KEYNOTE-868中，当KEYTRUDA联合化疗（紫杉醇和卡铂）治疗晚期或复发性子宫内膜癌（n=382）时，接受KEYTRUDA联合化疗的患者中有35%发生严重不良反应，而接受安慰剂联合化疗的患者中有19%（n=377）。

Fatal adverse reactions occurred in 1.6% of patients receiving KEYTRUDA in combination with chemotherapy, including COVID-19 (0.5%) and cardiac arrest (0.3%). KEYTRUDA was discontinued for an adverse reaction in 14% of patients. Adverse reactions occurring in patients treated with KEYTRUDA and chemotherapy were generally similar to those observed with KEYTRUDA alone or chemotherapy alone, with the exception of rash (33% all Grades; 2.9% Grades 3-4)..

接受KEYTRUDA联合化疗的患者中有1.6%发生致命不良反应，包括COVID-19（0.5%）和心脏骤停（0.3%）。KEYTRUDA因14%的患者出现不良反应而停药。接受KEYTRUDA和化疗的患者发生的不良反应通常与单独使用KEYTRUDA或单独使用化疗的患者相似，但皮疹除外（33%为所有级别；2.9%为3-4级）。。

In KEYNOTE-775, when KEYTRUDA was administered in combination with LENVIMA to patients with advanced endometrial carcinoma that was pMMR or not MSI-H (n=342), fatal adverse reactions occurred in 4.7% of patients. Serious adverse reactions occurred in 50% of these patients; the most common (≥3%) were hypertension (4.4%) and urinary tract infections (3.2%)..

在KEYNOTE-775中，当KEYTRUDA与LENVIMA联合用于pMMR或非MSI-H（n=342）的晚期子宫内膜癌患者时，4.7%的患者发生致命的不良反应。这些患者中有50%发生严重不良反应；最常见的（≥3%）是高血压（4.4%）和尿路感染（3.2%）。。

Discontinuation of KEYTRUDA due to an adverse reaction occurred in 15% of these patients. The most common adverse reaction leading to discontinuation of KEYTRUDA (≥1%) was increased ALT (1.2%).

这些患者中有15%因不良反应而停止使用KEYTRUDA。导致停用KEYTRUDA（≥1%）的最常见不良反应是ALT升高（1.2%）。

The most common adverse reactions for KEYTRUDA in combination with LENVIMA (reported in ≥20% patients) were hypothyroidism and hypertension (67% each), fatigue (58%), diarrhea (55%), musculoskeletal disorders (53%), nausea (49%), decreased appetite (44%), vomiting (37%), stomatitis (35%), abdominal pain and weight loss (34% each), urinary tract infections (31%), proteinuria (29%), constipation (27%), headache (26%), hemorrhagic events (25%), palmar-plantar erythrodysesthesia (23%), dysphonia (22%), and rash (20%)..

KEYTRUDA联合LENVIMA最常见的不良反应是甲状腺功能减退和高血压（各占67%）、疲劳（58%）、腹泻（55%）、肌肉骨骼疾病（53%）、恶心（49%）、食欲下降（44%）、呕吐（37%）、口腔炎（35%）、腹痛和体重减轻（各占34%）、尿路感染（31%）、蛋白尿（29%）、便秘（27%）、头痛（26%）、出血事件（25%）、掌底红细胞感觉异常（23%）、发声困难（22%）和皮疹（20%）。。

Adverse reactions occurring in patients with MSI-H or dMMR endometrial carcinoma who received KEYTRUDA as a single agent were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a single agent.

接受KEYTRUDA作为单一药物的MSI-H或dMMR子宫内膜癌患者发生的不良反应与接受KEYTRUDA作为单一药物的黑色素瘤或NSCLC患者发生的不良反应相似。

Adverse reactions occurring in patients with TMB-H cancer were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.

TMB-H癌症患者发生的不良反应与接受KEYTRUDA作为单一药物的其他实体瘤患者发生的不良反应相似。

Adverse reactions occurring in patients with recurrent or metastatic cSCC or locally advanced cSCC were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

复发或转移性cSCC或局部晚期cSCC患者发生的不良反应与接受KEYTRUDA作为单一疗法的黑色素瘤或NSCLC患者发生的不良反应相似。

In KEYNOTE-522, when KEYTRUDA was administered with neoadjuvant chemotherapy (carboplatin and paclitaxel followed by doxorubicin or epirubicin and cyclophosphamide) followed by surgery and continued adjuvant treatment with KEYTRUDA as a single agent (n=778) to patients with newly diagnosed, previously untreated, high-risk early-stage TNBC, fatal adverse reactions occurred in 0.9% of patients, including 1 each of adrenal crisis, autoimmune encephalitis, hepatitis, pneumonia, pneumonitis, pulmonary embolism, and sepsis in association with multiple organ dysfunction syndrome and myocardial infarction.

在KEYNOTE-522中，当KEYTRUDA接受新辅助化疗（卡铂和紫杉醇，然后是阿霉素或表柔比星和环磷酰胺），然后进行手术，并继续使用KEYTRUDA作为单一药物进行辅助治疗（n=778）时，0.9%的患者发生致命的不良反应，其中肾上腺危象，自身免疫性脑炎，肝炎，肺炎，肺炎，肺栓塞和脓毒症各1例，伴有多器官功能障碍综合征和心肌梗死。

Serious adverse reactions occurred in 44% of patients receiving KEYTRUDA; those ≥2% were febrile neutropenia (15%), pyrexia (3.7%), anemia (2.6%), and neutropenia (2.2%). KEYTRUDA was discontinued in 20% of patients due to adverse reactions. The most common reactions (≥1%) resulting in permanent discontinuation were increased ALT (2.7%), increased AST (1.5%), and rash (1%).

接受KEYTRUDA治疗的患者中有44%发生严重不良反应；那些≥2%的是发热性中性粒细胞减少症（15%），发热（3.7%），贫血（2.6%）和中性粒细胞减少症（2.2%）。由于不良反应，20%的患者停用了KEYTRUDA。导致永久停药的最常见反应（≥1%）是ALT升高（2.7%），AST升高（1.5%）和皮疹（1%）。

The most common adverse reactions (≥20%) in patients receiving KEYTRUDA were fatigue (70%), nausea (67%), alopecia (61%), rash (52%), constipation (42%), diarrhea and peripheral neuropathy (41% each), stomatitis (34%), vomiting (31%), headache (30%), arthralgia (29%), pyrexia (28%), cough (26%), abdominal pain (24%), decreased appetite (23%), insomnia (21%), and myalgia (20%)..

接受KEYTRUDA治疗的患者最常见的不良反应（≥20%）是疲劳（70%），恶心（67%），脱发（61%），皮疹（52%），便秘（42%），腹泻和周围神经病变（各41%），口腔炎（34%），呕吐（31%），头痛（30%），关节痛（29%），发热（28%），咳嗽（26%），腹痛（24%），食欲下降（23%），失眠（21%）和肌痛（20%）。。

In KEYNOTE-355, when KEYTRUDA and chemotherapy (paclitaxel, paclitaxel protein-bound, or gemcitabine and carboplatin) were administered to patients with locally recurrent unresectable or metastatic TNBC who had not been previously treated with chemotherapy in the metastatic setting (n=596), fatal adverse reactions occurred in 2.5% of patients, including cardio-respiratory arrest (0.7%) and septic shock (0.3%).

在KEYNOTE-355中，当KEYTRUDA和化疗（紫杉醇，紫杉醇蛋白结合或吉西他滨和卡铂）用于局部复发的不可切除或转移性TNBC患者，这些患者以前没有在转移性环境中接受过化疗（n=596），致命的不良反应发生在2.5%的患者中，包括心肺骤停（0.7%）和感染性休克（0.3%）。

Serious adverse reactions occurred in 30% of patients receiving KEYTRUDA in combination with chemotherapy; the serious reactions in ≥2% were pneumonia (2.9%), anemia (2.2%), and thrombocytopenia (2%). KEYTRUDA was discontinued in 11% of patients due to adverse reactions. The most common reactions resulting in permanent discontinuation (≥1%) were increased ALT (2.2%), increased AST (1.5%), and pneumonitis (1.2%).

接受KEYTRUDA联合化疗的患者中有30%发生严重不良反应；≥2%的严重反应是肺炎（2.9%），贫血（2.2%）和血小板减少症（2%）。由于不良反应，11%的患者停用了KEYTRUDA。导致永久停药（≥1%）的最常见反应是ALT升高（2.2%），AST升高（1.5%）和肺炎（1.2%）。

The most common adverse reactions (≥20%) in patients receiving KEYTRUDA in combination with chemotherapy were fatigue (48%), nausea (44%), alopecia (34%), diarrhea and constipation (28% each), vomiting and rash (26% each), cough (23%), decreased appetite (21%), and headache (20%)..

接受KEYTRUDA联合化疗的患者最常见的不良反应（≥20%）是疲劳（48%），恶心（44%），脱发（34%），腹泻和便秘（各28%），呕吐和皮疹（各26%），咳嗽（23%），食欲下降（21%）和头痛（20%）。。

Lactation

哺乳期

Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 4 months after the last dose.

由于母乳喂养的儿童可能会出现严重的不良反应，建议女性在治疗期间和最后一次给药后4个月内不要母乳喂养。

Pediatric Use

儿科使用

In KEYNOTE-051, 173 pediatric patients (65 pediatric patients aged 6 months to younger than 12 years and 108 pediatric patients aged 12 years to 17 years) were administered KEYTRUDA 2 mg/kg every 3 weeks. The median duration of exposure was 2.1 months (range: 1 day to 25 months).

在KEYNOTE-051中，每3周给173名儿科患者（65名6个月至12岁以下的儿科患者和108名12岁至17岁的儿科患者）服用KEYTRUDA 2 mg/kg。中位暴露时间为2.1个月（范围：1天至25个月）。

Adverse reactions that occurred at a ≥10% higher rate in pediatric patients when compared to adults were pyrexia (33%), leukopenia (31%), vomiting (29%), neutropenia (28%), headache (25%), abdominal pain (23%), thrombocytopenia (22%), Grade 3 anemia (17%), decreased lymphocyte count (13%), and decreased white blood cell count (11%)..

与成人相比，儿科患者发生率≥10%的不良反应为发热（33%），白细胞减少（31%），呕吐（29%），中性粒细胞减少（28%），头痛（25%），腹痛（23%），血小板减少（22%），3级贫血（17%），淋巴细胞计数减少（13%），白细胞计数减少（11%）。。

Geriatric Use

老年使用

Of the 564 patients with locally advanced or metastatic urothelial cancer treated with KEYTRUDA in combination with enfortumab vedotin, 44% (n=247) were 65-74 years and 26% (n=144) were 75 years or older. No overall differences in safety or effectiveness were observed between patients 65 years of age or older and younger patients.

在用KEYTRUDA联合enfortumab vedotin治疗的564例局部晚期或转移性尿路上皮癌患者中，44%（n=247）为65-74岁，26%（n=144）为75岁或以上。。

Patients 75 years of age or older treated with KEYTRUDA in combination with enfortumab vedotin experienced a higher incidence of fatal adverse reactions than younger patients. The incidence of fatal adverse reactions was 4% in patients younger than 75 and 7% in patients 75 years or older..

75岁或以上接受KEYTRUDA联合enfortumab vedotin治疗的患者比年轻患者发生致命不良反应的发生率更高。。。

Additional Selected KEYTRUDA Indications in the U.S.

美国其他选定的KEYTRUDA适应症。

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA联合铂和氟尿嘧啶（FU）用于转移性或不可切除的复发性头颈部鳞状细胞癌（HNSCC）患者的一线治疗。

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.

。

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.

KEYTRUDA作为单一药物，适用于治疗复发或转移性HNSCC患者，在含铂化疗期间或之后疾病进展。

Classical Hodgkin Lymphoma

经典霍奇金淋巴瘤

KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

。

KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.

KEYTRUDA适用于治疗难治性cHL的儿科患者，或在2种或更多种治疗方案后复发的cHL。

Primary Mediastinal Large B-Cell Lymphoma

原发性纵隔大B细胞淋巴瘤

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy..

KEYTRUDA适用于治疗成人和儿科难治性原发性纵隔大B细胞淋巴瘤（PMBCL）患者，或在2次或更多次治疗后复发的患者。不建议使用KEYTRUDA治疗需要紧急细胞减灭治疗的PMBCL患者。。

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

微卫星不稳定性高或错配修复缺陷型癌症

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options..

KEYTRUDA适用于治疗成人和儿科患者，这些患者具有不可切除或转移性微卫星不稳定性高（MSI-H）或错配修复缺陷（dMMR）实体瘤，这是由FDA批准的测试确定的，这些实体瘤在先前的治疗后已取得进展，并且没有令人满意的替代治疗选择。。

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

微卫星不稳定性高或错配修复缺陷型结直肠癌

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) as determined by an FDA-approved test.

根据FDA批准的测试，KEYTRUDA适用于治疗不可切除或转移性MSI-H或dMMR结直肠癌（CRC）患者。

Esophageal Cancer

食管癌

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:

KEYTRUDA适用于治疗局部晚期或转移性食管或胃食管交界处（GEJ）（震中高于GEJ 1至5厘米的肿瘤）癌症的患者，这些癌症不适合手术切除或确定性放化疗：

in combination with platinum- and fluoropyrimidine-based chemotherapy, or

联合铂类和氟嘧啶类化疗，或

as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test.

通过FDA批准的测试确定，在对表达PD-L1（CPS≥10）的鳞状细胞组织学肿瘤患者进行一种或多种先前的全身治疗后，作为单一药物。

Biliary Tract Cancer

胆道癌

KEYTRUDA, in combination with gemcitabine and cisplatin, is indicated for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer (BTC).

KEYTRUDA与吉西他滨和顺铂联合用于治疗局部晚期不可切除或转移性胆道癌（BTC）患者。

Merkel Cell Carcinoma

默克尔细胞癌

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).

KEYTRUDA适用于治疗复发性局部晚期或转移性Merkel细胞癌（MCC）的成人和儿科患者。

Renal Cell Carcinoma

肾细胞癌

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).

KEYTRUDA与阿西替尼联合用于成人晚期肾细胞癌（RCC）患者的一线治疗。

KEYTRUDA, in combination with lenvatinib, is indicated for the first-line treatment of adult patients with advanced RCC.

KEYTRUDA与lenvatinib联合用于晚期RCC成年患者的一线治疗。

KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.

KEYTRUDA适用于肾切除术后或肾切除术和转移性病变切除术后中高或高复发风险的RCC患者的辅助治疗。

Endometrial Carcinoma

子宫内膜癌

KEYTRUDA, in combination with carboplatin and paclitaxel, followed by KEYTRUDA as a single agent, is indicated for the treatment of adult patients with primary advanced or recurrent endometrial carcinoma.

KEYTRUDA联合卡铂和紫杉醇，然后作为单一药物，用于治疗成人原发性晚期或复发性子宫内膜癌患者。

KEYTRUDA, in combination with lenvatinib, is indicated for the treatment of adult patients with advanced endometrial carcinoma that is mismatch repair proficient (pMMR) as determined by an FDA-approved test or not MSI-H, who have disease progression following prior systemic therapy in any setting are not candidates for curative surgery or radiation..

KEYTRUDA与lenvatinib联合用于治疗晚期子宫内膜癌的成年患者，这些患者是通过FDA批准的测试或非MSI-H确定的错配修复熟练（pMMR），在任何情况下，在先前的全身治疗后都有疾病进展，不适合进行根治性手术或放疗。。

KEYTRUDA, as a single agent, is indicated for the treatment of adult patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation..

KEYTRUDA作为单一药物，适用于治疗成人晚期子宫内膜癌患者，即MSI-H或dMMR，这是由FDA批准的测试确定的，这些患者在任何情况下接受过全身治疗后都有疾病进展，并且不适合进行根治性手术或放疗。。

Tumor Mutational Burden-High Cancer

肿瘤突变负荷高的癌症

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options..

。。

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established..

根据肿瘤反应率和反应持久性，该适应症在加速批准下获得批准。继续批准该适应症可能取决于验证性试验中临床益处的验证和描述。KEYTRUDA在TMB-H中枢神经系统癌症儿科患者中的安全性和有效性尚未确定。。

Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf.

请参阅KEYTRUDA（pembrolizumab）的处方信息http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf和KEYTRUDA的药物指南http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf.

About LENVIMA® (lenvatinib); available as 10 mg and 4 mg capsules

关于乐伐替尼® （乐伐替尼）；有10mg和4mg胶囊两种

LENVIMA, discovered and developed by Eisai, is an orally available multiple receptor tyrosine kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4, the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET.

由Eisai发现和开发的LENVIMA是一种口服多受体酪氨酸激酶抑制剂，可抑制血管内皮生长因子（VEGF）受体VEGFR1（FLT1），VEGFR2（KDR）和VEGFR3（FLT4）的激酶活性。LENVIMA除了正常的细胞功能外，还抑制其他与致病性血管生成，肿瘤生长和癌症进展有关的激酶，包括成纤维细胞生长因子（FGF）受体FGFR1-4，血小板衍生生长因子受体α（PDGFRα），KIT和RET。

In syngeneic mouse tumor models, LENVIMA decreased tumor-associated macrophages, increased activated cytotoxic T cells, and demonstrated greater antitumor activity in combination with an anti-PD-1 monoclonal antibody compared to either treatment alone..

在同基因小鼠肿瘤模型中，与单独治疗相比，LENVIMA降低了肿瘤相关巨噬细胞，增加了活化的细胞毒性T细胞，并与抗PD-1单克隆抗体联合显示出更高的抗肿瘤活性。。

LENVIMA® (lenvatinib) Indications in the U.S.

LENVIMA® （乐伐替尼）在美国的适应症。

For the treatment of adult patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC).

用于治疗局部复发或转移性，进行性，放射性碘难治性分化型甲状腺癌（DTC）的成年患者。

In combination with pembrolizumab, for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).

与pembrolizumab联合用于成人晚期肾细胞癌（RCC）患者的一线治疗。

In combination with everolimus, for the treatment of adult patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy.

联合依维莫司治疗一次先前的抗血管生成治疗后的成年晚期肾细胞癌（RCC）患者。

For the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC).

。

In combination with pembrolizumab, for the treatment of patients with advanced endometrial carcinoma (EC) that is mismatch repair proficient (pMMR), as determined by an FDA-approved test, or not microsatellite instability-high (MSI-H), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation..

与pembrolizumab联合使用，用于治疗晚期子宫内膜癌（EC）患者，该患者通过FDA批准的测试确定为错配修复熟练（pMMR），或者不是微卫星不稳定性高（MSI-H），这些患者在任何情况下都有先前全身治疗后的疾病进展，并且不适合进行根治性手术或放疗。。

Selected Safety Information for LENVIMA

Warnings and Precautions

警告和注意事项

Hypertension. In differentiated thyroid cancer (DTC), hypertension occurred in 73% of patients on LENVIMA (44% grade 3-4). In advanced renal cell carcinoma (RCC), hypertension occurred in 42% of patients on LENVIMA + everolimus (13% grade 3). Systolic blood pressure ≥160 mmHg occurred in 29% of patients, and 21% had diastolic blood pressure ≥100 mmHg.

高血压。在分化型甲状腺癌（DTC）中，73%的LENVIMA患者发生高血压（44%为3-4级）。在晚期肾细胞癌（RCC）中，42%的LENVIMA+依维莫司患者发生高血压（13%为3级）。29%的患者收缩压≥160 mmHg，21%的患者舒张压≥100 mmHg。

In unresectable hepatocellular carcinoma (HCC), hypertension occurred in 45% of LENVIMA-treated patients (24% grade 3). Grade 4 hypertension was not reported in HCC..

在不可切除的肝细胞癌（HCC）中，45%的LENVIMA治疗患者（24%为3级）发生高血压。HCC中未报告4级高血压。。

Serious complications of poorly controlled hypertension have been reported. Control blood pressure prior to initiation. Monitor blood pressure after 1 week, then every 2 weeks for the first 2 months, and then at least monthly thereafter during treatment. Withhold and resume at reduced dose when hypertension is controlled or permanently discontinue based on severity..

据报道，高血压控制不佳的严重并发症。在开始之前控制血压。1周后监测血压，然后在前2个月每2周监测一次，然后在治疗期间至少每月监测一次。当高血压得到控制或根据严重程度永久停止时，停止并以减少的剂量恢复。。

Cardiac Dysfunction. Serious and fatal cardiac dysfunction can occur with LENVIMA. Across clinical trials in 799 patients with DTC, RCC, and HCC, grade 3 or higher cardiac dysfunction occurred in 3% of LENVIMA-treated patients. Monitor for clinical symptoms or signs of cardiac dysfunction. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity..

心脏功能障碍。LENVIMA可能会发生严重致命的心脏功能障碍。在799例DTC，RCC和HCC患者的临床试验中，3%的LENVIMA治疗患者发生3级或更高级别的心脏功能障碍。监测心脏功能障碍的临床症状或体征。恢复后以减少的剂量停止并恢复，或根据严重程度永久停止。。

Arterial Thromboembolic Events. Among patients receiving LENVIMA or LENVIMA + everolimus, arterial thromboembolic events of any severity occurred in 2% of patients in RCC and HCC and 5% in DTC. Grade 3-5 arterial thromboembolic events ranged from 2% to 3% across all clinical trials.

动脉血栓栓塞事件。在接受LENVIMA或LENVIMA+依维莫司治疗的患者中，2%的RCC和HCC患者发生任何严重程度的动脉血栓栓塞事件，5%的DTC患者发生动脉血栓栓塞事件。在所有临床试验中，3-5级动脉血栓栓塞事件的发生率为2%至3%。

Among patients receiving LENVIMA with KEYTRUDA, arterial thrombotic events of any severity occurred in 5% of patients in CLEAR, including myocardial infarction (3.4%) and cerebrovascular accident (2.3%).

。

Permanently discontinue following an arterial thrombotic event. The safety of resuming after an arterial thromboembolic event has not been established and LENVIMA has not been studied in patients who have had an arterial thromboembolic event within the previous 6 months.

动脉血栓形成事件后永久停止。动脉血栓栓塞事件后恢复的安全性尚未确定，LENVIMA尚未在过去6个月内发生动脉血栓栓塞事件的患者中进行研究。

Hepatotoxicity. Across clinical studies enrolling 1,327 LENVIMA-treated patients with malignancies other than HCC, serious hepatic adverse reactions occurred in 1.4% of patients. Fatal events, including hepatic failure, acute hepatitis and hepatorenal syndrome, occurred in 0.5% of patients. In HCC, hepatic encephalopathy occurred in 8% of LENVIMA-treated patients (5% grade 3-5).

肝毒性。在招募1327名LENVIMA治疗的HCC以外的恶性肿瘤患者的临床研究中，1.4%的患者发生了严重的肝脏不良反应。0.5%的患者发生致命事件，包括肝衰竭，急性肝炎和肝肾综合征。在HCC中，8%的LENVIMA治疗患者发生肝性脑病（5%为3-5级）。

Grade 3-5 hepatic failure occurred in 3% of LENVIMA-treated patients. 2% of patients discontinued LENVIMA due to hepatic encephalopathy and 1% discontinued due to hepatic failure..

3%的LENVIMA治疗患者发生3-5级肝衰竭。2%的患者因肝性脑病停用LENVIMA，1%因肝衰竭停用。。

Monitor liver function prior to initiation, then every 2 weeks for the first 2 months, and at least monthly thereafter during treatment. Monitor patients with HCC closely for signs of hepatic failure, including hepatic encephalopathy. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity..

。密切监测HCC患者的肝衰竭迹象，包括肝性脑病。恢复后以减少的剂量停止并恢复，或根据严重程度永久停止。。

Renal Failure or Impairment. Serious including fatal renal failure or impairment can occur with LENVIMA. Renal impairment was reported in 14% and 7% of LENVIMA-treated patients in DTC and HCC, respectively. Grade 3-5 renal failure or impairment occurred in 3% of patients with DTC and 2% of patients with HCC, including 1 fatal event in each study.

肾功能衰竭或损害。LENVIMA可能会发生严重的，包括致命的肾衰竭或损害。在DTC和HCC中，LENVIMA治疗的患者中分别有14%和7%报告了肾功能损害。3%的DTC患者和2%的HCC患者发生3-5级肾功能衰竭或损害，每项研究中包括1例致命事件。

In RCC, renal impairment or renal failure was reported in 18% of LENVIMA + everolimus–treated patients (10% grade 3)..

在肾细胞癌中，18%的LENVIMA+依维莫司治疗患者（10%为3级）报告肾功能不全或肾衰竭。。

Initiate prompt management of diarrhea or dehydration/hypovolemia. Withhold and resume at reduced dose upon recovery or permanently discontinue for renal failure or impairment based on severity.

立即处理腹泻或脱水/血容量不足。恢复后停止并以减少的剂量恢复，或根据严重程度因肾衰竭或损害而永久停药。

Proteinuria. In DTC and HCC, proteinuria was reported in 34% and 26% of LENVIMA-treated patients, respectively. Grade 3 proteinuria occurred in 11% and 6% in DTC and HCC, respectively. In RCC, proteinuria occurred in 31% of patients receiving LENVIMA + everolimus (8% grade 3). Monitor for proteinuria prior to initiation and periodically during treatment.

蛋白尿。在DTC和HCC中，分别有34%和26%的LENVIMA治疗患者报告有蛋白尿。DTC和HCC的3级蛋白尿发生率分别为11%和6%。在RCC中，接受LENVIMA+依维莫司治疗的患者中有31%发生蛋白尿（3级8%）。开始前和治疗期间定期监测蛋白尿。

If urine dipstick proteinuria ≥2+ is detected, obtain a 24-hour urine protein. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity..

如果检测到尿试纸蛋白尿≥2+，则获得24小时尿蛋白。恢复后以减少的剂量停止并恢复，或根据严重程度永久停止。。

Diarrhea. Of the 737 LENVIMA-treated patients in DTC and HCC, diarrhea occurred in 49% (6% grade 3). In RCC, diarrhea occurred in 81% of LENVIMA + everolimus–treated patients (19% grade 3). Diarrhea was the most frequent cause of dose interruption/reduction, and diarrhea recurred despite dose reduction.

腹泻。。在RCC中，81%的LENVIMA+依维莫司治疗患者发生腹泻（19%为3级）。腹泻是剂量中断/减少的最常见原因，尽管剂量减少，腹泻仍会复发。

Promptly initiate management of diarrhea. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity..

及时启动腹泻管理。恢复后以减少的剂量停止并恢复，或根据严重程度永久停止。。

Fistula Formation and Gastrointestinal Perforation. Of the 799 patients treated with LENVIMA or LENVIMA + everolimus in DTC, RCC, and HCC, fistula or gastrointestinal perforation occurred in 2%. Permanently discontinue in patients who develop gastrointestinal perforation of any severity or grade 3-4 fistula..

瘘管形成和胃肠穿孔。在DTC，RCC和HCC中用LENVIMA或LENVIMA+依维莫司治疗的799例患者中，瘘管或胃肠道穿孔发生率为2%。发生任何严重程度的胃肠道穿孔或3-4级瘘管的患者永久停药。。

QT Interval Prolongation. In DTC, QT/QTc interval prolongation occurred in 9% of LENVIMA-treated patients and QT interval prolongation of >500 ms occurred in 2%. In RCC, QTc interval increases of >60 ms occurred in 11% of patients receiving LENVIMA + everolimus and QTc interval >500 ms occurred in 6%.

。在DTC中，9%的LENVIMA治疗患者发生QT/QTc间期延长，2%的患者发生QT间期延长>500 ms。在RCC中，接受LENVIMA+依维莫司治疗的患者中有11%的QTc间隔增加>60 ms，而QTc间隔>500 ms的患者发生率为6%。

In HCC, QTc interval increases of >60 ms occurred in 8% of LENVIMA-treated patients and QTc interval >500 ms occurred in 2%..

在HCC中，8%的LENVIMA治疗患者的QTc间隔增加>60 ms，2%的患者QTc间隔>500 ms。。

Monitor and correct electrolyte abnormalities at baseline and periodically during treatment. Monitor electrocardiograms in patients with congenital long QT syndrome, congestive heart failure, bradyarrhythmias, or those who are taking drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics.

在基线和治疗期间定期监测和纠正电解质异常。监测先天性长QT综合征、充血性心力衰竭、缓慢性心律失常患者或服用已知延长QT间期药物（包括Ia类和III类抗心律失常药物）的患者的心电图。

Withhold and resume at reduced dose upon recovery based on severity..

根据严重程度恢复后，停止并以减少的剂量恢复。。

Hypocalcemia. In DTC, grade 3-4 hypocalcemia occurred in 9% of LENVIMA-treated patients. In 65% of cases, hypocalcemia improved or resolved following calcium supplementation with or without dose interruption or dose reduction. In RCC, grade 3-4 hypocalcemia occurred in 6% of LENVIMA + everolimus–treated patients.

低钙血症。在DTC中，9%的LENVIMA治疗患者发生3-4级低钙血症。在65%的病例中，低钙血症在补充钙后得到改善或解决，无论是否有剂量中断或剂量减少。在RCC中，LENVIMA+依维莫司治疗的患者中有6%发生3-4级低钙血症。

In HCC, grade 3 hypocalcemia occurred in 0.8% of LENVIMA-treated patients. Monitor blood calcium levels at least monthly and replace calcium as necessary during treatment. Withhold and resume at reduced dose upon recovery or permanently discontinue depending on severity..

。至少每月监测血钙水平，并在治疗期间根据需要更换钙。恢复后停止并以减少的剂量恢复，或根据严重程度永久停止。。

Reversible Posterior Leukoencephalopathy Syndrome (RPLS). Across clinical studies of 1,823 patients who received LENVIMA as a single agent, RPLS occurred in 0.3%. Confirm diagnosis of RPLS with MRI. Withhold and resume at reduced dose upon recovery or permanently discontinue depending on severity and persistence of neurologic symptoms..

可逆性后部白质脑病综合征（RPLS）。在1823名接受LENVIMA作为单一药物的患者的临床研究中，RPL发生率为0.3%。通过MRI确认RPLS的诊断。根据神经系统症状的严重程度和持续性，停止并在恢复后以减少的剂量恢复或永久停止。。

Hemorrhagic Events. Serious including fatal hemorrhagic events can occur with LENVIMA. In DTC, RCC, and HCC clinical trials, hemorrhagic events, of any grade, occurred in 29% of the 799 patients treated with LENVIMA as a single agent or in combination with everolimus. The most frequently reported hemorrhagic events (all grades and occurring in at least 5% of patients) were epistaxis and hematuria.

出血事件。LENVIMA可能发生严重的出血事件，包括致命的出血事件。在DTC，RCC和HCC临床试验中，799例使用LENVIMA作为单一药物或与依维莫司联合治疗的患者中，有29%发生了任何级别的出血事件。最常报告的出血事件（所有级别，至少5%的患者发生）是鼻出血和血尿。

In DTC, grade 3-5 hemorrhage occurred in 2% of LENVIMA-treated patients, including 1 fatal intracranial hemorrhage among 16 patients who received LENVIMA and had CNS metastases at baseline. In RCC, grade 3-5 hemorrhage occurred in 8% of LENVIMA + everolimus–treated patients, including 1 fatal cerebral hemorrhage.

在DTC中，2%的LENVIMA治疗患者发生3-5级出血，其中16例接受LENVIMA治疗并在基线时发生中枢神经系统转移的患者中有1例致命性颅内出血。在RCC中，LENVIMA+依维莫司治疗的患者中有8%发生3-5级出血，其中包括1例致命性脑出血。

In HCC, grade 3-5 hemorrhage occurred in 5% of LENVIMA-treated patients, including 7 fatal hemorrhagic events. Serious tumor-related bleeds, including fatal hemorrhagic events, occurred in LENVIMA-treated patients in clinical trials and in the postmarketing setting. In postmarketing surveillance, serious and fatal carotid artery hemorrhages were seen more frequently in patients with anaplastic thyroid carcinoma (ATC) than other tumors.

在HCC中，5%的LENVIMA治疗患者发生3-5级出血，包括7例致命的出血事件。在临床试验和上市后环境中，LENVIMA治疗的患者发生了严重的肿瘤相关出血，包括致命的出血事件。在上市后监测中，甲状腺未分化癌（ATC）患者比其他肿瘤更容易出现严重致命的颈动脉出血。

Safety and effectiveness of LENVIMA in patients with ATC have not been demonstrated in clinical trials..

LENVIMA在ATC患者中的安全性和有效性尚未在临床试验中得到证实。。

Consider the risk of severe or fatal hemorrhage associated with tumor invasion or infiltration of major blood vessels (eg, carotid artery). Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

考虑与肿瘤侵袭或主要血管（例如颈动脉）浸润相关的严重或致命出血的风险。恢复后以减少的剂量停止并恢复，或根据严重程度永久停止。

Impairment of Thyroid Stimulating Hormone Suppression/Thyroid Dysfunction. LENVIMA impairs exogenous thyroid suppression. In DTC, 88% of patients had baseline thyroid stimulating hormone (TSH) level ≤0.5 mU/L. In patients with normal TSH at baseline, elevation of TSH level >0.5 mU/L was observed post baseline in 57% of LENVIMA-treated patients.

促甲状腺激素抑制/甲状腺功能障碍受损。LENVIMA损害外源性甲状腺抑制。在DTC中，88%的患者基线促甲状腺激素（TSH）水平≤0.5 mU/L。在基线TSH正常的患者中，57%的LENVIMA治疗患者的TSH水平在基线后升高>0.5 mU/L。

In RCC and HCC, grade 1 or 2 hypothyroidism occurred in 24% of LENVIMA + everolimus–treated patients and 21% of LENVIMA-treated patients, respectively. In patients with normal or low TSH at baseline, elevation of TSH was observed post baseline in 70% of LENVIMA-treated patients in HCC and 60% of LENVIMA + everolimus–treated patients in RCC..

在RCC和HCC中，分别有24%的LENVIMA+依维莫司治疗患者和21%的LENVIMA治疗患者发生1级或2级甲状腺功能减退症。在基线TSH正常或低的患者中，70%的LENVIMA治疗的HCC患者和60%的LENVIMA+依维莫司治疗的RCC患者在基线后观察到TSH升高。。

Monitor thyroid function prior to initiation and at least monthly during treatment. Treat hypothyroidism according to standard medical practice.

在开始之前和治疗期间至少每月监测甲状腺功能。根据标准医疗实践治疗甲状腺功能减退症。

Impaired Wound Healing. Impaired wound healing has been reported in patients who received LENVIMA. Withhold LENVIMA for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of LENVIMA after resolution of wound healing complications has not been established..

伤口愈合受损。据报道，接受LENVIMA治疗的患者伤口愈合受损。在选择性手术前至少1周保留LENVIMA。大手术后至少2周内不要给药，直到伤口充分愈合。伤口愈合并发症解决后恢复LENVIMA的安全性尚未确定。。

Osteonecrosis of the Jaw (ONJ). ONJ has been reported in patients receiving LENVIMA. Concomitant exposure to other risk factors, such as bisphosphonates, denosumab, dental disease or invasive dental procedures, may increase the risk of ONJ.

颌骨坏死（ONJ）。。同时暴露于其他风险因素，如双膦酸盐，denosumab，牙科疾病或侵入性牙科手术，可能会增加ONJ的风险。

Perform an oral examination prior to treatment with LENVIMA and periodically during LENVIMA treatment. Advise patients regarding good oral hygiene practices and to consider having preventive dentistry performed prior to treatment with LENVIMA and throughout treatment with LENVIMA.

在使用LENVIMA治疗之前和LENVIMA治疗期间定期进行口腔检查。建议患者注意良好的口腔卫生习惯，并考虑在使用LENVIMA治疗之前和整个使用LENVIMA治疗期间进行预防性牙科治疗。

Avoid invasive dental procedures, if possible, while on LENVIMA treatment, particularly in patients at higher risk. Withhold LENVIMA for at least 1 week prior to scheduled dental surgery or invasive dental procedures, if possible. For patients requiring invasive dental procedures, discontinuation of bisphosphonate treatment may reduce the risk of ONJ..

如果可能的话，在使用LENVIMA治疗时，避免进行侵入性牙科手术，特别是在风险较高的患者中。如果可能的话，在预定的牙科手术或侵入性牙科手术之前，扣留LENVIMA至少1周。对于需要侵入性牙科手术的患者，停止双膦酸盐治疗可能会降低ONJ的风险。。

Withhold LENVIMA if ONJ develops and restart based on clinical judgement of adequate resolution.

如果ONJ发展并根据足够分辨率的临床判断重新启动，则扣留LENVIMA。

Embryo‐Fetal Toxicity. Based on its mechanism of action and data from animal reproduction studies, LENVIMA can cause fetal harm when administered to pregnant women. In animal reproduction studies, oral administration of LENVIMA during organogenesis at doses below the recommended clinical doses resulted in embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits.

胚胎-胎儿毒性。根据其作用机制和动物繁殖研究的数据，LENVIMA在给孕妇服用时会造成胎儿伤害。在动物繁殖研究中，在器官发生过程中以低于推荐临床剂量的剂量口服LENVIMA会导致大鼠和兔子的胚胎毒性，胎儿毒性和致畸性。

Advise pregnant women of the potential risk to a fetus; and advise females of reproductive potential to use effective contraception during treatment with LENVIMA and for 30 days after the last dose..

告知孕妇对胎儿的潜在风险；并建议有生殖潜力的女性在使用LENVIMA治疗期间和最后一剂后30天内使用有效的避孕措施。。

Adverse Reactions

不良反应

In DTC, the most common adverse reactions (≥30%) observed in LENVIMA-treated patients were hypertension (73%), fatigue (67%), diarrhea (67%), arthralgia/myalgia (62%), decreased appetite (54%), decreased weight (51%), nausea (47%), stomatitis (41%), headache (38%), vomiting (36%), proteinuria (34%), palmar-plantar erythrodysesthesia syndrome (32%), abdominal pain (31%), and dysphonia (31%).

在DTC中，在LENVIMA治疗的患者中观察到的最常见的不良反应（≥30%）是高血压（73%），疲劳（67%），腹泻（67%），关节痛/肌痛（62%），食欲下降（54%），体重下降（51%），恶心（47%），口腔炎（41%），头痛（38%），呕吐（36%），蛋白尿（34%），掌底红细胞感觉异常综合征（32%），腹痛（31%）和发音困难（31%）。

The most common serious adverse reactions (≥2%) were pneumonia (4%), hypertension (3%), and dehydration (3%). Adverse reactions led to dose reductions in 68% of LENVIMA-treated patients; 18% discontinued LENVIMA. The most common adverse reactions (≥10%) resulting in dose reductions were hypertension (13%), proteinuria (11%), decreased appetite (10%), and diarrhea (10%); the most common adverse reactions (≥1%) resulting in discontinuation of LENVIMA were hypertension (1%) and asthenia (1%)..

最常见的严重不良反应（≥2%）是肺炎（4%），高血压（3%）和脱水（3%）。不良反应导致68%的LENVIMA治疗患者的剂量减少；18%停止服用LENVIMA。导致剂量减少的最常见不良反应（≥10%）是高血压（13%），蛋白尿（11%），食欲下降（10%）和腹泻（10%）；导致停用LENVIMA的最常见不良反应（≥1%）是高血压（1%）和虚弱（1%）。。

In RCC, the most common adverse reactions (≥20%) observed in LENVIMA + KEYTRUDA-treated patients were fatigue (63%), diarrhea (62%), musculoskeletal pain (58%), hypothyroidism (57%), hypertension (56%), stomatitis (43%), decreased appetite (41%), rash (37%), nausea (36%), decreased weight (30%), dysphonia (30%), proteinuria (30%), palmar-plantar erythrodysesthesia syndrome (29%), abdominal pain (27%), hemorrhagic events (27%), vomiting (26%), constipation (25%), hepatotoxicity (25%), headache (23%), and acute kidney injury (21%).Fatal adverse reactions occurred in 4.3% of patients receiving LENVIMA in combination with KEYTRUDA, including cardio-respiratory arrest (0.9%), sepsis (0.9%), and one case (0.3%) each of arrhythmia, autoimmune hepatitis, dyspnea, hypertensive crisis, increased blood creatinine, multiple organ dysfunction syndrome, myasthenic syndrome, myocarditis, nephritis, pneumonitis, ruptured aneurysm and subarachnoid hemorrhage.

在RCC中，在LENVIMA+KEYTRUDA治疗的患者中观察到的最常见的不良反应（≥20%）是疲劳（63%），腹泻（62%），肌肉骨骼疼痛（58%），甲状腺功能减退（57%），高血压（56%），口腔炎（43%），食欲下降（41%），皮疹（37%），恶心（36%），体重下降（30%），发音困难（30%），蛋白尿（30%），掌底红细胞感觉异常综合征（29%），腹痛（27%），出血事件（27%），呕吐（26%），便秘（25%），肝毒性（25%），头痛（23%）和急性肾损伤（21%）。4.3%接受LENVIMA联合KEYTRUDA治疗的患者发生致命不良反应，包括心肺骤停（0.9%），败血症（0.9%），心律失常，自身免疫性肝炎，呼吸困难，高血压危象，血肌酐升高，多器官功能障碍综合征，肌无力综合征，心肌炎，肾炎，肺炎，动脉瘤破裂和蛛网膜下腔出血各1例（0.3%）。

Serious adverse reactions occurred in 51% of patients receiving LENVIMA and KEYTRUDA. Serious adverse reactions in ≥2% of patients were hemorrhagic events (5%), diarrhea (4%), hypertension (3%), myocardial infarction (3%), pneumonitis (3%), vomiting (3%), acute kidney injury (2%), adrenal insufficiency (2%), dyspnea (2%), and pneumonia (2%).Permanent discontinuation of LENVIMA, KEYTRUDA, or both due to an adverse reaction occurred in 37% of patients; 26% LENVIMA only, 29% KEYTRUDA only, and 13% both drugs.

51%接受LENVIMA和KEYTRUDA治疗的患者发生严重不良反应。≥2%的患者严重不良反应为出血事件（5%），腹泻（4%），高血压（3%），心肌梗塞（3%），肺炎（3%），呕吐（3%），急性肾损伤（2%），肾上腺功能不全（2%），呼吸困难（2%）和肺炎（2%）。37%的患者因不良反应而永久停用LENVIMA，KEYTRUDA或两者；仅26%的LENVIMA，仅29%的KEYTRUDA，以及13%的两种药物。

The most common adverse reactions (≥2%) leading to permanent discontinuation of LENVIMA, KEYTRUDA, or both were pneumonitis (3%), myocardial infarction (3%), hepatotoxicity (3%), acute kidney injury (3%), rash (3%), and diarrhea (2%). Dose interruptions of LENVIMA, KEYTRUDA, or both due to an adverse reaction occurred in 78% of p.

导致LENVIMA，KEYTRUDA或两者永久停药的最常见不良反应（≥2%）是肺炎（3%），心肌梗塞（3%），肝毒性（3%），急性肾损伤（3%），皮疹（3%）和腹泻（2%）。由于不良反应，LENVIMA，KEYTRUDA或两者的剂量中断发生在p的78%。

In RCC, the most common adverse reactions (≥30%) observed in LENVIMA + everolimus–treated patients were diarrhea (81%), fatigue (73%), arthralgia/myalgia (55%), decreased appetite (53%), vomiting (48%), nausea (45%), stomatitis (44%), hypertension (42%), peripheral edema (42%), cough (37%), abdominal pain (37%), dyspnea (35%), rash (35%), decreased weight (34%), hemorrhagic events (32%), and proteinuria (31%).

在RCC中，LENVIMA+依维莫司治疗的患者最常见的不良反应（≥30%）是腹泻（81%），疲劳（73%），关节痛/肌痛（55%），食欲下降（53%），呕吐（48%），恶心（45%），口腔炎（44%），高血压（42%），外周水肿（42%），咳嗽（37%），腹痛（37%），呼吸困难（35%），皮疹（35%），体重减轻（34%），出血事件（32%）和蛋白尿（31%）。

The most common serious adverse reactions (≥5%) were renal failure (11%), dehydration (10%), anemia (6%), thrombocytopenia (5%), diarrhea (5%), vomiting (5%), and dyspnea (5%). Adverse reactions led to dose reductions or interruption in 89% of patients. The most common adverse reactions (≥5%) resulting in dose reductions were diarrhea (21%), fatigue (8%), thrombocytopenia (6%), vomiting (6%), nausea (5%), and proteinuria (5%).

最常见的严重不良反应（≥5%）是肾功能衰竭（11%），脱水（10%），贫血（6%），血小板减少症（5%），腹泻（5%），呕吐（5%）和呼吸困难（5%）。不良反应导致89%的患者剂量减少或中断。导致剂量减少的最常见不良反应（≥5%）是腹泻（21%），疲劳（8%），血小板减少（6%），呕吐（6%），恶心（5%）和蛋白尿（5%）。

Treatment discontinuation due to an adverse reaction occurred in 29% of patients..

29%的患者因不良反应而停止治疗。。

In HCC, the most common adverse reactions (≥20%) observed in LENVIMA-treated patients were hypertension (45%), fatigue (44%), diarrhea (39%), decreased appetite (34%), arthralgia/myalgia (31%), decreased weight (31%), abdominal pain (30%), palmar-plantar erythrodysesthesia syndrome (27%), proteinuria (26%), dysphonia (24%), hemorrhagic events (23%), hypothyroidism (21%), and nausea (20%).

在HCC中，在LENVIMA治疗的患者中观察到的最常见的不良反应（≥20%）是高血压（45%），疲劳（44%），腹泻（39%），食欲下降（34%），关节痛/肌痛（31%），体重下降（31%），腹痛（30%），掌底红细胞感觉异常综合征（27%），蛋白尿（26%），发音困难（24%），出血事件（23%），甲状腺功能减退（21%）和恶心（20%）。

The most common serious adverse reactions (≥2%) were hepatic encephalopathy (5%), hepatic failure (3%), ascites (3%), and decreased appetite (2%). Adverse reactions led to dose reductions or interruption in 62% of patients. The most common adverse reactions (≥5%) resulting in dose reductions were fatigue (9%), decreased appetite (8%), diarrhea (8%), proteinuria (7%), hypertension (6%), and palmar-plantar erythrodysesthesia syndrome (5%).

最常见的严重不良反应（≥2%）是肝性脑病（5%），肝衰竭（3%），腹水（3%）和食欲下降（2%）。不良反应导致62%的患者剂量减少或中断。导致剂量减少的最常见不良反应（≥5%）是疲劳（9%），食欲下降（8%），腹泻（8%），蛋白尿（7%），高血压（6%）和掌底红细胞感觉异常综合征（5%）。

Treatment discontinuation due to an adverse reaction occurred in 20% of patients. The most common adverse reactions (≥1%) resulting in discontinuation of LENVIMA were fatigue (1%), hepatic encephalopathy (2%), hyperbilirubinemia (1%), and hepatic failure (1%)..

20%的患者因不良反应而停止治疗。导致停用LENVIMA的最常见不良反应（≥1%）是疲劳（1%），肝性脑病（2%），高胆红素血症（1%）和肝衰竭（1%）。。

In endometrial carcinoma, the most common adverse reactions (≥20%) observed in LENVIMA + KEYTRUDA-treated patients were hypothyroidism (67%), hypertension (67%), fatigue (58%), diarrhea (55%), musculoskeletal disorders (53%), nausea (49%), decreased appetite (44%), vomiting (37%), stomatitis (35%), decreased weight (34%), abdominal pain (34%), urinary tract infection (31%), proteinuria (29%), constipation (27%), headache (26%), hemorrhagic events (25%), palmar-plantar erythrodysesthesia (23%), dysphonia (22%), and rash (20%).

在子宫内膜癌中，在LENVIMA+KEYTRUDA治疗的患者中观察到的最常见的不良反应（≥20%）是甲状腺功能减退（67%），高血压（67%），疲劳（58%），腹泻（55%），肌肉骨骼疾病（53%），恶心（49%），食欲下降（44%），呕吐（37%），口腔炎（35%），体重减轻（34%），腹痛（34%），尿路感染（31%），蛋白尿（29%），便秘（27%），头痛（26%），出血事件（25%），掌底红细胞感觉异常（23%），发音困难（22%）和皮疹（20%）。

Fatal adverse reactions among these patients occurred in 4.7% of those treated with LENVIMA and KEYTRUDA, including 2 cases of pneumonia, and 1 case of the following: acute kidney injury, acute myocardial infarction, colitis, decreased appetite, intestinal perforation, lower gastrointestinal hemorrhage, malignant gastrointestinal obstruction, multiple organ dysfunction syndrome, myelodysplastic syndrome, pulmonary embolism, and right ventricular dysfunction.

这些患者中致命的不良反应发生率为LENVIMA和KEYTRUDA治疗组的4.7%，其中包括2例肺炎，以及以下1例：急性肾损伤，急性心肌梗死，结肠炎，食欲下降，肠穿孔，下消化道出血，恶性胃肠道梗阻，多器官功能障碍综合征，骨髓增生异常综合征，肺栓塞和右心室功能障碍。

Serious adverse reactions occurred in 50% of these patients receiving LENVIMA and KEYTRUDA. Serious adverse reactions with frequency ≥3% were hypertension (4.4%), and urinary tract infection (3.2%). Discontinuation of LENVIMA due to an adverse reaction occurred in 26% of these patients. The most common (≥1%) adverse reactions leading to discontinuation of LENVIMA were hypertension (2%), asthenia (1.8%), diarrhea (1.2%), decreased appetite (1.2%), proteinuria (1.2%), and vomiting (1.2%).

接受LENVIMA和KEYTRUDA治疗的患者中有50%发生严重不良反应。频率≥3%的严重不良反应为高血压（4.4%）和尿路感染（3.2%）。26%的患者因不良反应而停止服用LENVIMA。导致停用LENVIMA的最常见（≥1%）不良反应是高血压（2%），虚弱（1.8%），腹泻（1.2%），食欲下降（1.2%），蛋白尿（1.2%）和呕吐（1.2%）。

Dose reductions of LENVIMA due to adverse reactions occurred in 67% of patients. The most common (≥5%) adverse reactions resulting in dose reduction of LENVIMA were hypertension (18%), diarrhea (11%), palmar-plantar erythrodysesthesia syndrome (9%), proteinuria (7%), fatigue (7%), decreased appetite (6%), asthen.

67%的患者因不良反应而减少了LENVIMA的剂量。导致LENVIMA剂量减少的最常见（≥5%）不良反应是高血压（18%），腹泻（11%），掌底红细胞感觉异常综合征（9%），蛋白尿（7%），疲劳（7%），食欲下降（6%），虚弱。

Use in Specific Populations

在特定人群中使用

Because of the potential for serious adverse reactions in breastfed children, advise women to discontinue breastfeeding during treatment and for 1 week after last dose. LENVIMA may impair fertility in males and females of reproductive potential.

由于母乳喂养的儿童可能会出现严重的不良反应，建议女性在治疗期间和最后一次给药后1周内停止母乳喂养。LENVIMA可能会损害具有生殖潜力的男性和女性的生育能力。

No dose adjustment is recommended for patients with mild (creatine clearance [CLcr] 60-89 mL/min) or moderate (CLcr 30-59 mL/min) renal impairment. LENVIMA concentrations may increase in patients with DTC, RCC, or endometrial carcinoma and severe (CLcr 15-29 mL/min) renal impairment. Reduce the dose for patients with DTC, RCC, or endometrial carcinoma and severe renal impairment.

对于轻度（肌酸清除率[CLcr]60-89 mL/min）或中度（CLcr 30-59 mL/min）肾功能不全的患者，不建议调整剂量。DTC，RCC或子宫内膜癌和严重（CLcr 15-29 mL/min）肾功能不全患者的LENVIMA浓度可能会增加。减少DTC，RCC或子宫内膜癌和严重肾功能不全患者的剂量。

There is no recommended dose for patients with HCC and severe renal impairment. LENVIMA has not been studied in patients with end stage renal disease..

HCC和严重肾功能不全患者没有推荐剂量。LENVIMA尚未在终末期肾病患者中进行研究。。

No dose adjustment is recommended for patients with HCC and mild hepatic impairment (Child-Pugh A). There is no recommended dose for patients with HCC with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment. No dose adjustment is recommended for patients with DTC, RCC, or endometrial carcinoma and mild or moderate hepatic impairment.

对于HCC和轻度肝损伤（Child-Pugh A）患者，不建议调整剂量。对于中度（Child-Pugh B）或重度（Child-Pugh C）肝功能损害的HCC患者，没有推荐剂量。对于DTC，RCC或子宫内膜癌以及轻度或中度肝功能损害的患者，不建议调整剂量。

LENVIMA concentrations may increase in patients with DTC, RCC, or endometrial carcinoma and severe hepatic impairment. Reduce the dose for patients with DTC, RCC, or endometrial carcinoma and severe hepatic impairment..

DTC，RCC或子宫内膜癌和严重肝损伤患者的LENVIMA浓度可能会增加。减少DTC，RCC或子宫内膜癌和严重肝损伤患者的剂量。。

Please see Prescribing Information for LENVIMA (lenvatinib) at http://www.lenvima.com/pdfs/prescribing-information.pdf.

请参阅LENVIMA（lenvatinib）的处方信息http://www.lenvima.com/pdfs/prescribing-information.pdf.

About LYNPARZA® (olaparib)

关于LYNPARZA®（olaparib）

LYNPARZA is a first-in-class PARP inhibitor and the first targeted treatment to potentially exploit DNA damage response (DDR) pathway deficiencies, such as BRCA mutations, to preferentially kill cancer cells. Inhibition of PARP with LYNPARZA leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death.

LYNPARZA是一流的PARP抑制剂，也是第一种可能利用DNA损伤反应（DDR）途径缺陷（如BRCA突变）优先杀死癌细胞的靶向治疗。用LYNPARZA抑制PARP导致与DNA单链断裂结合的PARP被捕获，复制叉停滞，它们的崩溃以及DNA双链断裂和癌细胞死亡的产生。

LYNPARZA is being tested in a range of tumor types with defects and dependencies in the DDR..

LYNPARZA正在一系列肿瘤类型中进行测试，这些肿瘤类型在DDR中存在缺陷和依赖性。。

LYNPARZA, which is being jointly developed and commercialized by AstraZeneca and Merck, has a broad clinical trial development program, and AstraZeneca and Merck are working together to understand how it may affect multiple PARP-dependent tumors as a monotherapy and in combination across multiple cancer types..

。。

INDICATIONS

适应症

LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:

LYNPARZA是一种聚（ADP-核糖）聚合酶（PARP）抑制剂，表明：

First-Line Maintenance BRCAm Advanced Ovarian Cancer

一线维护BRCAm晚期卵巢癌

For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA..

用于维持治疗对一线铂类化疗完全或部分反应的有害或疑似有害种系或体细胞BRCA突变（gBRCAm或sBRCAm）晚期上皮性卵巢癌，输卵管癌或原发性腹膜癌的成年患者。根据FDA批准的LYNPARZA伴随诊断选择患者进行治疗。。

First-Line Maintenance HRD-Positive Advanced Ovarian Cancer in Combination with Bevacizumab

In combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD)-positive status defined by either:.

与贝伐单抗联合用于维持治疗晚期上皮性卵巢癌，输卵管癌或原发性腹膜癌的成年患者，这些患者对一线铂类化疗完全或部分有反应，并且其癌症与同源重组缺陷（HRD）相关，阳性状态由以下任一定义：。

a deleterious or suspected deleterious BRCA mutation, and/or

有害或疑似有害的BRCA突变，和/或

genomic instability

基因组不稳定性

Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

根据FDA批准的LYNPARZA伴随诊断选择患者进行治疗。

Maintenance BRCA-mutated Recurrent Ovarian Cancer

维持BRCA突变的复发性卵巢癌

For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA..

用于维持治疗对铂类化疗完全或部分反应的有害或疑似有害种系或体细胞BRCA突变（gBRCAm或sBRCAm）复发性上皮性卵巢癌，输卵管癌或原发性腹膜癌的成年患者。根据FDA批准的LYNPARZA伴随诊断选择患者进行治疗。。

Adjuvant Treatment of gBRCAm, HER2-Negative, High-Risk Early Breast Cancer

gBRCAm、HER2阴性、高危早期乳腺癌的辅助治疗

For the adjuvant treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA..

对于已接受新辅助或辅助化疗的有害或疑似有害gBRCAm，人表皮生长因子受体2（HER2）阴性高危早期乳腺癌的成年患者的辅助治疗。根据FDA批准的LYNPARZA伴随诊断选择患者进行治疗。。

gBRCAm, HER2-Negative Metastatic Breast Cancer

gBRCAm，HER2阴性转移性乳腺癌

For the treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy.

用于治疗在新辅助，辅助或转移环境中接受化疗的有害或疑似有害gBRCAm，人表皮生长因子受体2（HER2）阴性转移性乳腺癌的成年患者。激素受体（HR）阳性乳腺癌患者应事先接受内分泌治疗，或被认为不适合进行内分泌治疗。

Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA..

根据FDA批准的LYNPARZA伴随诊断选择患者进行治疗。。

First-Line Maintenance gBRCAm Metastatic Pancreatic Cancer

一线维持gBRCAm转移性胰腺癌

For the maintenance treatment of adult patients with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA..

用于维持治疗患有有害或疑似有害gBRCAm转移性胰腺癌的成年患者，其疾病在一线铂类化疗方案的至少16周内尚未进展。根据FDA批准的LYNPARZA伴随诊断选择患者进行治疗。。

HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer

HRR基因突变的转移性去势抵抗性前列腺癌

For the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA..

用于治疗患有有害或疑似有害种系或体细胞同源重组修复（HRR）基因突变的转移性去势抵抗性前列腺癌（mCRPC）的成年患者，这些患者在先前用恩扎鲁胺或阿比特龙治疗后已进展。根据FDA批准的LYNPARZA伴随诊断选择患者进行治疗。。

BRCAm Metastatic Castration-Resistant Prostate Cancer in Combination with Abiraterone and Prednisone or Prednisolone

BRCAm转移性去势抵抗性前列腺癌联合阿比特龙、泼尼松或泼尼松龙

In combination with abiraterone and prednisone or prednisolone (abi/pred) for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC). Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA..

联合阿比特龙和泼尼松龙或泼尼松龙（abi/pred）治疗有害或疑似有害BRCA突变（BRCAm）转移性去势抵抗性前列腺癌（mCRPC）的成年患者。根据FDA批准的LYNPARZA伴随诊断选择患者进行治疗。。

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

禁忌症

There are no contraindications for LYNPARZA.

LYNPARZA没有禁忌症。

WARNINGS AND PRECAUTIONS

警告和注意事项

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in approximately 1.2% of patients with various BRCAm, gBRCAm, HRR gene-mutated or HRD-positive cancers who received LYNPARZA as a single agent or as part of a combination regimen, consistent with the approved indications, and the majority of events had a fatal outcome.

骨髓增生异常综合征/急性髓细胞白血病（MDS/AML）：大约1.2%的患有各种BRCAm，gBRCAm，HRR基因突变或HRD阳性癌症的患者接受LYNPARZA作为单一药物或作为联合方案的一部分，符合批准的适应症，并且大多数事件具有致命的结果。

The median duration of therapy in patients who developed MDS/AML was approximately 2 years (range: <6 months to >4 years). All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy..

MDS/AML患者的中位治疗时间约为2年（范围：<6个月至>4年）。所有这些患者都曾接受过铂类药物和/或其他DNA损伤剂的化疗，包括放疗。。

In SOLO-1, patients with newly diagnosed advanced BRCAm ovarian cancer, the incidence of MDS/AML was 1.9% (5/260) in patients who received LYNPARZA and 0.8% (1/130) in patients who received placebo based on an updated analysis. In PAOLA-1, of patients with newly diagnosed advanced ovarian cancer with HRD-positive status, the incidence of MDS/AML was 1.6% (4/255) in patients who received LYNPARZA and 2.3% (3/131) in the control arm..

在SOLO-1中，新诊断的晚期BRCAm卵巢癌患者中，接受LYNPARZA治疗的患者MDS/AML发生率为1.9%（5/260），接受安慰剂治疗的患者MDS/AML发生率为0.8%（1/130）。。。

In SOLO-2, patients with BRCAm platinum-sensitive relapsed ovarian cancer, the incidence of MDS/AML was 8% (15/195) in patients who received LYNPARZA and 4% (4/99) in patients who received placebo. The duration of LYNPARZA treatment prior to the diagnosis of MDS/AML ranged from 0.6 years to 4.5 years..

在SOLO-2中，BRCAm铂敏感复发性卵巢癌患者中，接受LYNPARZA治疗的患者MDS/AML发生率为8%（15/195），接受安慰剂治疗的患者MDS/AML发生率为4%（4/99）。在诊断为MDS/AML之前，LYNPARZA治疗的持续时间为0.6年至4.5年。。

Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood count weekly until recovery..

在患者从先前化疗引起的血液学毒性（≤1级）恢复之前，不要开始使用LYNPARZA。在基线时监测全血细胞计数的血细胞减少症，此后每月监测治疗期间的临床显着变化。对于长期的血液学毒性，中断LYNPARZA并每周监测血细胞计数直至恢复。。

If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.

如果4周后水平仍未恢复到1级或更低，请将患者转介给血液学家进行进一步检查，包括骨髓分析和细胞遗传学血液样本。如果MDS/AML得到确认，停止使用LYNPARZA。

Pneumonitis: Occurred in 0.8% of patients exposed to LYNPARZA monotherapy, and some cases were fatal. If patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt LYNPARZA treatment and initiate prompt investigation.

肺炎：暴露于LYNPARZA单一疗法的患者中有0.8%发生肺炎，有些病例是致命的。如果患者出现新的或恶化的呼吸道症状，如呼吸困难，咳嗽和发烧，或发生放射学异常，请中断LYNPARZA治疗并立即进行调查。

Discontinue LYNPARZA if pneumonitis is confirmed and treat patient appropriately..

如果确诊肺炎，停止使用LYNPARZA，并对患者进行适当治疗。。

Venous Thromboembolism (VTE): Including severe or fatal pulmonary embolism (PE) occurred in patients treated with LYNPARZA. In the combined data of two randomized, placebo-controlled clinical studies (PROfound and PROpel) in patients with metastatic castration-resistant prostate cancer (N=1180), VTE occurred in 8% of patients who received LYNPARZA, including pulmonary embolism in 6%.

静脉血栓栓塞（VTE）：包括用LYNPARZA治疗的患者发生严重或致命的肺栓塞（PE）。在转移性去势抵抗性前列腺癌患者（N=1180）的两项随机，安慰剂对照临床研究（深刻和推进）的综合数据中，接受LYNPARZA治疗的患者中有8%发生VTE，其中肺栓塞发生率为6%。

In the control arms, VTE occurred in 2.5%, including pulmonary embolism in 1.5%. Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism, and treat as medically appropriate, which may include long-term anticoagulation as clinically indicated..

在对照组中，VTE发生率为2.5%，其中肺栓塞发生率为1.5%。监测患者静脉血栓形成和肺栓塞的体征和症状，并根据医学需要进行治疗，其中可能包括临床指示的长期抗凝治疗。。

Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. Verify pregnancy status in females of reproductive potential prior to initiating treatment.

胚胎-胎儿毒性：根据其作用机制和在动物中的发现，LYNPARZA可引起胎儿伤害。在开始治疗之前，验证具有生殖潜力的女性的妊娠状况。

Females

女性

Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months following the last dose.

建议女性注意对胎儿的潜在风险的生殖潜力，并在治疗期间和最后一次给药后6个月内使用有效的避孕措施。

Males

男性

Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 3 months following the last dose of LYNPARZA and to not donate sperm during this time.

建议有生殖潜能女性伴侣或怀孕的男性患者在治疗期间和最后一剂LYNPARZA后3个月内使用有效的避孕方法，在此期间不要捐献精子。

ADVERSE REACTIONS—First-Line Maintenance BRCAm Advanced Ovarian Cancer

不良反应一线维持治疗BRCAm晚期卵巢癌

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the first-line maintenance setting for SOLO-1 were: nausea (77%), fatigue (67%), abdominal pain (45%), vomiting (40%), anemia (38%), diarrhea (37%), constipation (28%), upper respiratory tract infection/influenza/nasopharyngitis/bronchitis (28%), dysgeusia (26%), decreased appetite (20%), dizziness (20%), neutropenia (17%), dyspepsia (17%), dyspnea (15%), leukopenia (13%), urinary tract infection (13%), thrombocytopenia (11%), and stomatitis (11%)..

在SOLO-1一线维护环境中接受LYNPARZA治疗的患者中，≥10%的患者最常见的不良反应（1-4级）是：恶心（77%），疲劳（67%），腹痛（45%），呕吐（40%），贫血（38%），腹泻（37%），便秘（28%），上呼吸道感染/流感/鼻咽炎/支气管炎（28%），味觉障碍（26%），食欲下降（20%），头晕（20%），中性粒细胞减少（17%），消化不良（17%），呼吸困难（15%），白细胞减少（13%），尿路感染（13%），血小板减少（11%）和口腔炎（11%）。。

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the first-line maintenance setting for SOLO-1 were: decrease in hemoglobin (87%), increase in mean corpuscular volume (87%), decrease in leukocytes (70%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), decrease in platelets (35%), and increase in serum creatinine (34%)..

在SOLO-1一线维护环境中接受LYNPARZA治疗的患者中，≥25%的患者最常见的实验室异常（1-4级）是：血红蛋白减少（87%），平均红细胞体积增加（87%），白细胞减少（70%），淋巴细胞减少（67%），绝对中性粒细胞计数减少（51%），血小板减少（35%），血清肌酐增加（34%）。。

ADVERSE REACTIONS—First-Line Maintenance Advanced Ovarian Cancer in Combination with Bevacizumab

Most common adverse reactions (Grades 1-4) in ≥10% of patients treated with LYNPARZA/bevacizumab and at a ≥5% frequency compared to placebo/bevacizumab in the first-line maintenance setting for PAOLA-1 were: nausea (53%), fatigue (including asthenia) (53%), anemia (41%), lymphopenia (24%), vomiting (22%), and leukopenia (18%).

在PAOLA-1的一线维持治疗中，与安慰剂/贝伐单抗相比，接受LYNPARZA/贝伐单抗治疗的患者中≥10%的患者最常见的不良反应（1-4级）为：恶心（53%），疲劳（包括虚弱）（53%），贫血（41%），淋巴细胞减少（24%），呕吐（22%）和白细胞减少（18%）。

In addition, the most common adverse reactions (≥10%) for patients receiving LYNPARZA/bevacizumab irrespective of the frequency compared with the placebo/bevacizumab arm were: diarrhea (18%), neutropenia (18%), urinary tract infection (15%), and headache (14%)..

此外，与安慰剂/贝伐单抗组相比，接受LYNPARZA/贝伐单抗治疗的患者最常见的不良反应（≥10%）是：腹泻（18%），中性粒细胞减少（18%），尿路感染（15%）和头痛（14%）。。

In addition, venous thromboembolic events occurred more commonly in patients receiving LYNPARZA/bevacizumab (5%) than in those receiving placebo/bevacizumab (1.9%).

此外，接受LYNPARZA/贝伐单抗治疗的患者（5%）比接受安慰剂/贝伐单抗治疗的患者（1.9%）更常发生静脉血栓栓塞事件。

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients for LYNPARZA in combination with bevacizumab in the first-line maintenance setting for PAOLA-1 were: decrease in hemoglobin (79%), decrease in lymphocytes (63%), increase in serum creatinine (61%), decrease in leukocytes (59%), decrease in absolute neutrophil count (35%), and decrease in platelets (35%)..

在PAOLA-1的一线维持治疗中，≥25%的LYNPARZA联合贝伐单抗患者最常见的实验室异常（1-4级）是：血红蛋白减少（79%），淋巴细胞减少（63%），血清肌酐增加（61%），白细胞减少（59%），绝对中性粒细胞计数减少（35%）和血小板减少（35%）。。

ADVERSE REACTIONS—Maintenance gBRCAm Recurrent Ovarian Cancer

不良反应维持gBRCAm复发性卵巢癌

Most common adverse reactions (Grades 1-4) in ≥20% of patients who received LYNPARZA in the maintenance setting for SOLO-2 were: nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%), nasopharyngitis/upper respiratory tract infection (URI)/influenza (36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache (26%), decreased appetite (22%), and stomatitis (20%)..

在SOLO-2维持治疗中接受LYNPARZA治疗的患者中，≥20%的患者最常见的不良反应（1-4级）是：恶心（76%），疲劳（包括虚弱）（66%），贫血（44%），呕吐（37%），鼻咽炎/上呼吸道感染（URI）/流感（36%），腹泻（33%），关节痛/肌痛（30%），味觉障碍（27%），头痛（26%），食欲下降（22%）和口腔炎（20%）。。

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the maintenance setting for SOLO-2 were: increase in mean corpuscular volume (89%), decrease in hemoglobin (83%), decrease in leukocytes (69%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), increase in serum creatinine (44%), and decrease in platelets (42%)..

在SOLO-2维持治疗中接受LYNPARZA治疗的患者中，≥25%的患者最常见的实验室异常（1-4级）是：平均红细胞体积增加（89%），血红蛋白减少（83%），白细胞减少（69%），淋巴细胞减少（67%），绝对中性粒细胞计数减少（51%），血清肌酐增加（44%）和血小板减少（42%）。。

ADVERSE REACTIONS—Adjuvant Treatment of gBRCAm, HER2-Negative, High-Risk Early Breast Cancer

不良反应gBRCAm、HER2阴性、高危早期乳腺癌的辅助治疗

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the adjuvant setting for OlympiA were: nausea (57%), fatigue (including asthenia) (42%), anemia (24%), vomiting (23%), headache (20%), diarrhea (18%), leukopenia (17%), neutropenia (16%), decreased appetite (13%), dysgeusia (12%), dizziness (11%), and stomatitis (10%)..

在奥林匹亚辅助治疗中接受LYNPARZA治疗的患者中，≥10%的患者最常见的不良反应（1-4级）是：恶心（57%），疲劳（包括虚弱）（42%），贫血（24%），呕吐（23%），头痛（20%），腹泻（18%），白细胞减少（17%），中性粒细胞减少（16%），食欲下降（13%），味觉障碍（12%），头晕（11%）和口腔炎（10%）。。

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the adjuvant setting for OlympiA were: decrease in lymphocytes (77%), increase in mean corpuscular volume (67%), decrease in hemoglobin (65%), decrease in leukocytes (64%), and decrease in absolute neutrophil count (39%)..

在奥林匹亚辅助治疗中接受LYNPARZA治疗的患者中，≥25%的患者最常见的实验室异常（1-4级）是：淋巴细胞减少（77%），平均红细胞体积增加（67%），血红蛋白减少（65%），白细胞减少（64%），绝对中性粒细胞计数减少（39%）。。

ADVERSE REACTIONS—gBRCAm, HER2-Negative Metastatic Breast Cancer

不良反应gBRCAm，HER2阴性转移性乳腺癌

Most common adverse reactions (Grades 1-4) in ≥20% of patients who received LYNPARZA in the metastatic setting for OlympiAD were: nausea (58%), anemia (40%), fatigue (including asthenia) (37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhea (21%), and headache (20%)..

在奥运会转移性环境中接受LYNPARZA治疗的患者中，≥20%的患者最常见的不良反应（1-4级）是：恶心（58%），贫血（40%），疲劳（包括虚弱）（37%），呕吐（30%），中性粒细胞减少症（27%），呼吸道感染（27%），白细胞减少症（25%），腹泻（21%）和头痛（20%）。。

Most common laboratory abnormalities (Grades 1-4) in >25% of patients who received LYNPARZA in the metastatic setting for OlympiAD were: decrease in hemoglobin (82%), decrease in lymphocytes (73%), decrease in leukocytes (71%), increase in mean corpuscular volume (71%), decrease in absolute neutrophil count (46%), and decrease in platelets (33%)..

在奥运会转移性环境中接受LYNPARZA治疗的患者中，>25%的患者最常见的实验室异常（1-4级）是：血红蛋白减少（82%），淋巴细胞减少（73%），白细胞减少（71%），平均红细胞体积增加（71%），绝对中性粒细胞计数减少（46%）和血小板减少（33%）。。

ADVERSE REACTIONS—First-Line Maintenance gBRCAm Metastatic Pancreatic Adenocarcinoma

不良反应一线维持gBRCAm转移性胰腺癌

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the first-line maintenance setting for POLO were: fatigue (60%), nausea (45%), abdominal pain (34%), diarrhea (29%), anemia (27%), decreased appetite (25%), constipation (23%), vomiting (20%), back pain (19%), arthralgia (15%), rash (15%), thrombocytopenia (14%), dyspnea (13%), neutropenia (12%), nasopharyngitis (12%), dysgeusia (11%), and stomatitis (10%)..

在POLO一线维护环境中接受LYNPARZA治疗的患者中，≥10%的患者最常见的不良反应（1-4级）是：疲劳（60%），恶心（45%），腹痛（34%），腹泻（29%），贫血（27%），食欲下降（25%），便秘（23%），呕吐（20%），背痛（19%），关节痛（15%），皮疹（15%），血小板减少（14%），呼吸困难（13%），中性粒细胞减少（12%），鼻咽炎（12%），味觉障碍（11%）和口腔炎（10%）。。

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the first-line maintenance setting for POLO were: increase in serum creatinine (99%), decrease in hemoglobin (86%), increase in mean corpuscular volume (71%), decrease in lymphocytes (61%), decrease in platelets (56%), decrease in leukocytes (50%), and decrease in absolute neutrophil count (25%)..

在POLO一线维护环境中接受LYNPARZA治疗的患者中，≥25%的患者最常见的实验室异常（1-4级）是：血清肌酐升高（99%），血红蛋白降低（86%），平均红细胞体积增加（71%），淋巴细胞减少（61%），血小板减少（56%），白细胞减少（50%），绝对中性粒细胞计数减少（25%）。。

ADVERSE REACTIONS—HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer

不良反应-HRR基因突变的转移性去势抵抗性前列腺癌

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA for PROfound were: anemia (46%), fatigue (including asthenia) (41%), nausea (41%), decreased appetite (30%), diarrhea (21%), vomiting (18%), thrombocytopenia (12%), cough (11%), and dyspnea (10%).

接受LYNPARZA治疗的患者中，≥10%的患者最常见的不良反应（1-4级）是：贫血（46%），疲劳（包括虚弱）（41%），恶心（41%），食欲下降（30%），腹泻（21%），呕吐（18%），血小板减少症（12%），咳嗽（11%）和呼吸困难（10%）。

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA for PROfound were: decrease in hemoglobin (98%), decrease in lymphocytes (62%), decrease in leukocytes (53%), and decrease in absolute neutrophil count (34%).

接受LYNPARZA治疗的患者中，≥25%的患者最常见的实验室异常（1-4级）是：血红蛋白减少（98%），淋巴细胞减少（62%），白细胞减少（53%），绝对中性粒细胞减少计数（34%）。

ADVERSE REACTIONS—Metastatic Castration-Resistant Prostate Cancer in Combination with Abiraterone and Prednisone or Prednisolone

不良反应转移性去势抵抗性前列腺癌联合阿比特龙和泼尼松或泼尼松龙

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA/abiraterone with a difference of ≥5% compared to placebo for PROpel were: anemia (48%), fatigue (including asthenia) (38%), nausea (30%), diarrhea (19%), decreased appetite (16%), lymphopenia (14%), dizziness (14%), and abdominal pain (13%).

接受LYNPARZA/阿比特龙治疗的患者中，≥10%的患者最常见的不良反应（1-4级）与安慰剂相比差异≥5%，其中PROpel为：贫血（48%），疲劳（包括虚弱）（38%），恶心（30%），腹泻（19%），食欲下降（16%），淋巴细胞减少（14%），头晕（14%）和腹痛（13%）。

Most common laboratory abnormalities (Grades 1-4) in ≥20% of patients who received LYNPARZA/abiraterone for PROpel were: decrease in hemoglobin (97%), decrease in lymphocytes (70%), decrease in platelets (23%), and decrease in absolute neutrophil count (23%)..

接受LYNPARZA/阿比特龙治疗PROpel的患者中，≥20%的患者最常见的实验室异常（1-4级）是：血红蛋白减少（97%），淋巴细胞减少（70%），血小板减少（23%），绝对中性粒细胞计数减少（23%）。。

DRUG INTERACTIONS

Anticancer Agents: Clinical studies of LYNPARZA with other myelosuppressive anticancer agents, including DNA-damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.

抗癌药物：LYNPARZA与其他骨髓抑制性抗癌药物（包括DNA损伤剂）的临床研究表明，骨髓抑制毒性增强和延长。

CYP3A Inhibitors: Avoid coadministration of strong or moderate CYP3A inhibitors when using LYNPARZA. If a strong or moderate CYP3A inhibitor must be coadministered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment..

CYP3A抑制剂：使用LYNPARZA时，避免共同服用强或中度CYP3A抑制剂。如果必须共同服用强效或中度CYP3A抑制剂，请减少LYNPARZA的剂量。建议患者在LYNPARZA治疗期间避免使用葡萄柚、葡萄柚汁、塞维利亚橙汁和塞维利亚橙汁。。

CYP3A Inducers: Avoid coadministration of strong or moderate CYP3A inducers when using LYNPARZA.

CYP3A诱导剂：使用LYNPARZA时，避免共同使用强或中等CYP3A诱导剂。

USE IN SPECIFIC POPULATIONS

在特定人群中使用

Lactation: No data are available regarding the presence of olaparib in human milk, its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in the breastfed infant, advise a lactating woman not to breastfeed during treatment with LYNPARZA and for 1 month after receiving the final dose..

哺乳期：没有关于母乳中奥拉帕尼的存在及其对母乳喂养婴儿或产奶量的影响的数据。由于母乳喂养的婴儿可能会产生严重的不良反应，因此建议哺乳期妇女在服用LYNPARZA期间以及服用最终剂量后1个月内不要母乳喂养。。

Pediatric Use: The safety and efficacy of LYNPARZA have not been established in pediatric patients.

儿科用途：LYNPARZA的安全性和有效性尚未在儿科患者中确定。

Hepatic Impairment: No adjustment to the starting dose is required in patients with mild or moderate hepatic impairment (Child-Pugh classification A and B). There are no data in patients with severe hepatic impairment (Child-Pugh classification C).

肝损伤：轻度或中度肝损伤患者（Child-Pugh A类和B类）不需要调整起始剂量。没有严重肝功能损害患者的数据（Child-Pugh C级）。

Renal Impairment: No dosage modification is recommended in patients with mild renal impairment (CLcr 51-80 mL/min estimated by Cockcroft-Gault). In patients with moderate renal impairment (CLcr 31-50 mL/min), reduce the dose of LYNPARZA to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr ≤30 mL/min)..

肾功能损害：轻度肾功能损害患者（Cockcroft-Gault估计CLcr 51-80 mL/min）不建议调整剂量。对于中度肾功能不全（CLcr 31-50 mL/min）的患者，每天两次将LYNPARZA的剂量减少至200 mg。没有严重肾功能不全或终末期肾病（CLcr≤30 mL/min）患者的数据。。

Please see complete Prescribing Information, including Medication Guide.

请参阅完整的处方信息，包括用药指南。

About WELIREG® (belzutifan) 40 mg tablets, for oral use

关于WELIREG®（belzutifan）40 mg口服片剂

Indications in the U.S.

美国的适应症。

Certain von Hippel-Lindau (VHL) disease-associated tumors

某些von Hippel-Lindau（VHL）疾病相关肿瘤

WELIREG (belzutifan) is indicated for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery.

WELIREG（belzutifan）适用于治疗成年von Hippel-Lindau（VHL）疾病患者，这些患者需要治疗相关的肾细胞癌（RCC），中枢神经系统（CNS）血管母细胞瘤或胰腺神经内分泌肿瘤（pNET），不需要立即手术。

Advanced Renal Cell Carcinoma (RCC)

晚期肾细胞癌（RCC）

WELIREG is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) following a programmed death receptor-1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI).

WELIREG适用于程序性死亡受体-1（PD-1）或程序性死亡配体1（PD-L1）抑制剂和血管内皮生长因子酪氨酸激酶抑制剂（VEGF-TKI）治疗成人晚期肾细胞癌（RCC）患者。

Selected Safety Information for WELIREG

为WELIREG选择的安全信息

Warning: Embryo-Fetal Toxicity

Exposure to WELIREG during pregnancy can cause embryo-fetal harm. Verify pregnancy status prior to the initiation of WELIREG. Advise patients of these risks and the need for effective non-hormonal contraception as WELIREG can render some hormonal contraceptives ineffective.

怀孕期间接触WELIREG会导致胚胎-胎儿伤害。在开始WELIREG之前验证妊娠状态。告知患者这些风险以及需要有效的非激素避孕药，同时也可能导致一些激素避孕药无效。

Anemia

贫血

WELIREG can cause severe anemia that can require blood transfusion. Monitor for anemia before initiation of, and periodically throughout, treatment. Transfuse patients as clinically indicated. For patients with hemoglobin <8 g/dL, withhold WELIREG until ≥8 g/dL, then resume at the same or reduced dose or permanently discontinue WELIREG, depending on the severity of anemia.

韦利雷可导致严重贫血，需要输血。在开始治疗之前和整个治疗过程中定期监测贫血。根据临床指示为患者输血。对于血红蛋白<8 g/dL的患者，根据贫血的严重程度，保留WELIREG直至≥8 g/dL，然后以相同或减少的剂量恢复或永久停止WELIREG。

For life-threatening anemia or when urgent intervention is indicated, withhold WELIREG until hemoglobin ≥8 g/dL, then resume at a reduced dose or permanently discontinue WELIREG..

对于危及生命的贫血或需要紧急干预时，停止服用WELIREG，直到血红蛋白≥8 g/dL，然后减少剂量或永久停用WELIREG。。

In LITESPARK-004 (N=61), decreased hemoglobin occurred in 93% of patients with VHL disease and 7% had Grade 3 events. Median time to onset of anemia was 31 days (range: 1 day to 8.4 months).

在LITESPARK-004（N=61）中，93%的VHL患者血红蛋白降低，7%的患者发生3级事件。贫血发作的中位时间为31天（范围：1天至8.4个月）。

The safety of erythropoiesis-stimulating agents (ESAs) for treatment of anemia in patients with VHL disease treated with WELIREG has not been established.

红细胞生成刺激剂（ESAs）治疗用WELIREG治疗的VHL疾病患者贫血的安全性尚未确定。

In LITESPARK-005 (n=372), decreased hemoglobin occurred in 88% of patients with advanced RCC and 29% had Grade 3 events. Median time to onset of anemia was 29 days (range: 1 day to 16.6 months). Of the patients with anemia, 22% received transfusions only, 20% received ESAs only, and 12% received both transfusion and ESAs..

在LITESPARK-005（n=372）中，88%的晚期RCC患者血红蛋白降低，29%的患者发生3级事件。贫血发作的中位时间为29天（范围：1天至16.6个月）。在贫血患者中，22%仅接受输血，20%仅接受ESA，12%同时接受输血和ESA。。

Hypoxia

缺氧

WELIREG can cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization.

WELIREG可能导致严重缺氧，可能需要停药，补充氧气或住院治疗。

Monitor oxygen saturation before initiation of, and periodically throughout, treatment. For decreased oxygen saturation with exercise (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg), consider withholding WELIREG until pulse oximetry with exercise is greater than 88%, then resume at the same or a reduced dose.

在开始治疗之前和整个治疗过程中定期监测血氧饱和度。对于运动时血氧饱和度降低（例如，脉搏血氧仪<88%或PaO2≤55 mm Hg），考虑停止WELIREG，直到运动时脉搏血氧仪大于88%，然后以相同或减少的剂量恢复。

For decreased oxygen saturation at rest (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg) or when urgent intervention is indicated, withhold WELIREG until resolved and resume at a reduced dose or discontinue. For life-threatening or recurrent symptomatic hypoxia, permanently discontinue WELIREG. Advise patients to report signs and symptoms of hypoxia immediately to a healthcare provider..

对于静息时血氧饱和度降低（例如，脉搏血氧仪<88%或PaO2≤55 mm Hg）或需要紧急干预时，停止服用WELIREG直至解决，并以减少的剂量恢复或停止服用。对于危及生命或反复出现症状性缺氧，请永久停用WELIREG。建议患者立即向医疗保健提供者报告缺氧的迹象和症状。。

In LITESPARK-004, hypoxia occurred in 1.6% of patients.

在LITESPARK-004中，1.6%的患者发生缺氧。

In LITESPARK-005, hypoxia occurred in 15% of patients and 10% had Grade 3 events. Of the patients with hypoxia, 69% were treated with oxygen therapy. Median time to onset of hypoxia was 30.5 days (range: 1 day to 21.1 months).

在LITESPARK-005中，15%的患者发生缺氧，10%的患者发生3级事件。在缺氧患者中，69%接受了氧疗。缺氧发作的中位时间为30.5天（范围：1天至21.1个月）。

Embryo-Fetal Toxicity

Based on findings in animals, WELIREG can cause fetal harm when administered to a pregnant woman.

根据对动物的研究结果，WELIREG给孕妇服用时会对胎儿造成伤害。

Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. WELIREG can render some hormonal contraceptives ineffective.

告知孕妇和女性生殖潜力对胎儿的潜在风险。建议有生殖潜力的女性在用WELIREG治疗期间和最后一剂后1周内使用有效的非激素避孕。WELIREG可以使一些激素避孕药无效。

Advise male patients with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose..

建议有生殖潜力的女性伴侣的男性患者在接受WELIREG治疗期间以及最后一剂后1周内使用有效的避孕措施。。

Adverse Reactions

不良反应

In LITESPARK-004, serious adverse reactions occurred in 15% of patients, including anemia, hypoxia, anaphylaxis reaction, retinal detachment, and central retinal vein occlusion (1 patient each).

在LITESPARK-004中，15%的患者发生严重不良反应，包括贫血，缺氧，过敏反应，视网膜脱离和视网膜中央静脉阻塞（各1例）。

WELIREG was permanently discontinued due to adverse reactions in 3.3% of patients for dizziness and opioid overdose (1.6% each).

由于3.3%的患者出现头晕和阿片类药物过量的不良反应（各1.6%），WELIREG永久停药。

Dosage interruptions due to an adverse reaction occurred in 39% of patients. Those which required dosage interruption in >2% of patients were fatigue, decreased hemoglobin, anemia, nausea, abdominal pain, headache, and influenza-like illness.

39%的患者因不良反应而中断剂量。超过2%的患者需要中断剂量的是疲劳，血红蛋白降低，贫血，恶心，腹痛，头痛和流感样疾病。

Dose reductions due to an adverse reaction occurred in 13% of patients. The most frequently reported adverse reaction which required dose reduction was fatigue (7%).

13%的患者因不良反应而减少剂量。需要减少剂量的最常报告的不良反应是疲劳（7%）。

The most common adverse reactions (≥25%), including laboratory abnormalities, that occurred in patients who received WELIREG were decreased hemoglobin (93%), fatigue (64%), increased creatinine (64%), headache (39%), dizziness (38%), increased glucose (34%), and nausea (31%).

接受WELIREG治疗的患者最常见的不良反应（≥25%），包括实验室异常，包括血红蛋白降低（93%），疲劳（64%），肌酐升高（64%），头痛（39%），头晕（38%），血糖升高（34%）和恶心（31%）。

In LITESPARK-005, serious adverse reactions occurred in 38% of patients. The most frequently reported serious adverse reactions were hypoxia (7%), anemia (5%), pneumonia (3.5%), hemorrhage (3%), and pleural effusion (2.2%). Fatal adverse reactions occurred in 3.2% of patients who received WELIREG, including sepsis (0.5%) and hemorrhage (0.5%)..

在LITESPARK-005中，38%的患者发生严重不良反应。最常报告的严重不良反应是缺氧（7%），贫血（5%），肺炎（3.5%），出血（3%）和胸腔积液（2.2%）。接受WELIREG治疗的患者中有3.2%发生致命不良反应，包括败血症（0.5%）和出血（0.5%）。。

WELIREG was permanently discontinued due to adverse reactions in 6% of patients. Adverse reactions which resulted in permanent discontinuation (≥0.5%) were hypoxia (1.1%) and hemorrhage (0.5%).

由于6%的患者出现不良反应，WELIREG永久停药。导致永久停药（≥0.5%）的不良反应为缺氧（1.1%）和出血（0.5%）。

Dosage interruptions due to an adverse reaction occurred in 39% of patients. Of the patients who received WELIREG, 28% were 65 to 74 years, and 10% were 75 years and over. Dose interruptions occurred in 48% of patients ≥65 years of age and in 34% of younger patients. Adverse reactions which required dosage interruption in ≥2% of patients were anemia (8%), hypoxia (5%), COVID-19 (4.3%), fatigue (3.2%), and hemorrhage (2.2%)..

39%的患者因不良反应而中断剂量。在接受WELIREG的患者中，28%为65至74岁，10%为75岁及以上。48%≥65岁的患者和34%的年轻患者发生剂量中断。需要中断≥2%患者剂量的不良反应为贫血（8%），缺氧（5%），COVID-19（4.3%），疲劳（3.2%）和出血（2.2%）。。

Dose reductions due to an adverse reaction occurred in 13% of patients. Dose reductions occurred in 18% of patients ≥65 years of age and in 10% of younger patients. The most frequently reported adverse reactions which required dose reduction (≥1.0%) were hypoxia (5%) and anemia (3.2%).

13%的患者因不良反应而减少剂量。18%的≥65岁患者和10%的年轻患者发生剂量减少。需要减少剂量（≥1.0%）的最常报告的不良反应是缺氧（5%）和贫血（3.2%）。

The most common (≥25%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (88%), fatigue (43%), musculoskeletal pain (33%), increased creatinine (34%), decreased lymphocytes (34%), increased alanine aminotransferase (32%), decreased sodium (31%), increased potassium (29%), and increased aspartate aminotransferase (27%)..

最常见的（≥25%）不良反应，包括实验室异常，是血红蛋白降低（88%），疲劳（43%），肌肉骨骼疼痛（33%），肌酐升高（34%），淋巴细胞减少（34%），丙氨酸转氨酶升高（32%），钠降低（31%），钾升高（29%），天冬氨酸转氨酶升高（27%）。。

Drug Interactions

药物相互作用

Coadministration of WELIREG with inhibitors of UGT2B17 or CYP2C19 increases plasma exposure of belzutifan, which may increase the incidence and severity of adverse reactions. Monitor for anemia and hypoxia and reduce the dosage of WELIREG as recommended.

WELIREG与UGT2B17或CYP2C19抑制剂的共同给药增加了belzutifan的血浆暴露，这可能会增加不良反应的发生率和严重程度。监测贫血和缺氧，并根据建议减少WELIREG的剂量。

Coadministration of WELIREG with CYP3A4 substrates decreases concentrations of CYP3A4 substrates, which may reduce the efficacy of these substrates or lead to therapeutic failures. Avoid coadministration with sensitive CYP3A4 substrates. If coadministration cannot be avoided, increase the sensitive CYP3A4 substrate dosage in accordance with its Prescribing Information.

WELIREG与CYP3A4底物的共同给药会降低CYP3A4底物的浓度，这可能会降低这些底物的功效或导致治疗失败。避免与敏感的CYP3A4底物共同给药。如果无法避免共同给药，请根据其处方信息增加敏感的CYP3A4底物剂量。

Coadministration of WELIREG with hormonal contraceptives may lead to contraceptive failure or an increase in breakthrough bleeding..

WELIREG与激素避孕药的共同给药可能导致避孕失败或突破性出血增加。。

Lactation

哺乳期

Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with WELIREG and for 1 week after the last dose.

由于母乳喂养的儿童可能会产生严重的不良反应，因此建议女性在接受WELIREG治疗期间以及最后一次服用后1周内不要母乳喂养。

Females and Males of Reproductive Potential

生殖潜力的女性和男性

WELIREG can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to initiating treatment with WELIREG.

WELIREG给孕妇服用时会对胎儿造成伤害。在开始用WELIREG治疗之前，验证具有生殖潜力的女性的妊娠状况。

Use of WELIREG may reduce the efficacy of hormonal contraceptives. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose..

使用WELIREG可能会降低激素避孕药的功效。建议有生殖潜力的女性在用WELIREG治疗期间和最后一剂后1周内使用有效的非激素避孕。建议有生殖潜力的女性伴侣的男性在接受WELIREG治疗期间和最后一剂后1周内使用有效的避孕措施。。

Based on findings in animals, WELIREG may impair fertility in males and females of reproductive potential and the reversibility of this effect is unknown.

根据动物的研究结果，韦利雷可能会损害具有生殖潜力的雄性和雌性的生育能力，这种影响的可逆性尚不清楚。

Pediatric Use

儿科使用

Safety and effectiveness of WELIREG in pediatric patients under 18 years of age have not been established.

WELIREG在18岁以下儿科患者中的安全性和有效性尚未确定。

Please see Prescribing Information, including information for the Boxed Warning about embryo-fetal toxicity, for WELIREG (belzutifan) at https://www.merck.com/product/usa/pi_circulars/w/welireg/welireg_pi.pdf and Medication Guide for WELIREG at https://www.merck.com/product/usa/pi_circulars/w/welireg/welireg_mg.pdf..

请参阅WELIREG（belzutifan）的处方信息，包括关于胚胎-胎儿毒性的盒装警告信息https://www.merck.com/product/usa/pi_circulars/w/welireg/welireg_pi.pdf和WELIREG的药物指南https://www.merck.com/product/usa/pi_circulars/w/welireg/welireg_mg.pdf..

About the Merck and Eisai strategic collaboration

关于默克和卫材的战略合作

In March 2018, Eisai and Merck, known as MSD outside of the United States and Canada, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of LENVIMA. Under the agreement, the companies jointly develop, manufacture and commercialize LENVIMA, both as monotherapy and in combination with Merck’s anti-PD-1 therapy KEYTRUDA.

2018年3月，卫材和默克（在美国和加拿大以外被称为MSD）通过一家附属公司，就LENVIMA的全球共同开发和共同商业化进行了战略合作。根据该协议，两家公司共同开发、制造和商业化LENVIMA，既可以作为单一疗法，也可以与默克公司的抗PD-1疗法KEYTRUDA联合使用。

Eisai and Merck are studying the KEYTRUDA plus LENVIMA combination through the LEAP (LEnvatinib And Pembrolizumab) clinical program in various tumor types across multiple clinical trials..

Eisai和Merck正在通过LEAP（LEnvatinib和Pembrolizumab）临床计划研究KEYTRUDA加LENVIMA组合在多种临床试验中的各种肿瘤类型。。

About the AstraZeneca and Merck strategic oncology collaboration

关于阿斯利康和默克战略肿瘤学合作

In July 2017, AstraZeneca and Merck, known as MSD outside of the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialize certain oncology products including LYNPARZA, the world’s first PARP inhibitor, for multiple cancer types. Working together, the companies will develop these products in combination with other potential new medicines and as monotherapies.

2017年7月，阿斯利康（AstraZeneca）和默克（Merck）（在美国和加拿大以外被称为MSD）宣布了一项全球战略肿瘤学合作，以共同开发和共同商业化某些肿瘤学产品，包括世界上第一种PARP抑制剂LYNPARZA，用于多种癌症类型。。

Independently, the companies will develop these oncology products in combination with their respective PD-L1 and PD-1 medicines..

独立地，这些公司将结合各自的PD-L1和PD-1药物开发这些肿瘤学产品。。

About the Astellas, Pfizer and Merck collaboration

关于Astellas、辉瑞和默克的合作

Astellas and Seagen entered a clinical collaboration agreement with Merck to evaluate the combination of Astellas’ and Seagen’s Padcev® (enfortumab vedotin-ejfv) and Merck’s KEYTRUDA® (pembrolizumab) in patients with previously untreated metastatic urothelial cancer. Padcev® and the Padcev device are trademarks jointly owned by Agensys, Inc., and Seagen Inc.

Astellas和Seagen与默克公司签订了临床合作协议，以评估Astellas和Seagen的Padcev®（enfortumab vedotin ejfv）和默克的KEYTRUDA®（pembrolizumab）在先前未经治疗的转移性尿路上皮癌患者中的组合。。

Pfizer Inc. completed its acquisition of Seagen on December 14, 2023..

辉瑞公司于2023年12月14日完成了对Seagen的收购。。

About the Daiichi Sankyo and Merck collaboration

关于第一三共和默克的合作

Daiichi Sankyo and Merck entered into a global collaboration in October 2023 to jointly develop and commercialize patritumab deruxtecan (HER3-DXd), ifinatamab deruxtecan (I-DXd) and raludotatug deruxtecan (R-DXd), except in Japan where Daiichi Sankyo will maintain exclusive rights. Daiichi Sankyo will be solely responsible for manufacturing and supply..

2023年10月，第一三共与默克公司达成全球合作，共同开发和商业化patritumab deruxtecan（HER3 DXd）、ifinatamab deruxtecan（I-DXd）和raludotatug deruxtecan（R-DXd），但在日本，第一三共将保留专有权。。。

Merck’s focus on cancer

默克专注于癌症

Every day, we follow the science as we work to discover innovations that can help patients, no matter what stage of cancer they have. As a leading oncology company, we are pursuing research where scientific opportunity and medical need converge, underpinned by our diverse pipeline of more than 25 novel mechanisms.

每天，我们都在遵循科学，努力发现可以帮助患者的创新，无论他们处于癌症的哪个阶段。作为一家领先的肿瘤学公司，我们正在寻求科学机会和医疗需求相融合的研究，并以我们超过25种新型机制的多样化渠道为基础。

With one of the largest clinical development programs across more than 30 tumor types, we strive to advance breakthrough science that will shape the future of oncology. By addressing barriers to clinical trial participation, screening and treatment, we work with urgency to reduce disparities and help ensure patients have access to high-quality cancer care.

凭借跨越30多种肿瘤类型的最大临床开发项目之一，我们努力推进突破性科学，这将塑造肿瘤学的未来。通过解决临床试验参与，筛查和治疗的障碍，我们迫切需要减少差异，并帮助确保患者获得高质量的癌症护理。

Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer. For more information, visit https://www.merck.com/research/oncology..

我们坚定不移的承诺将使我们更接近为更多癌症患者带来生命的目标。有关更多信息，请访问https://www.merck.com/research/oncology..

About Merck

默克

At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines.

在美国和加拿大以外被称为MSD的默克公司，我们的目标是团结一致的：我们利用尖端科学的力量来拯救和改善世界各地的生活。130多年来，我们通过开发重要的药物和疫苗给人类带来了希望。

We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities.

。我们培养了一支多元化和包容性的全球劳动力队伍，并每天负责任地运作，为所有人和社区创造一个安全、可持续和健康的未来。

For more information, visit www.merck.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn..

有关更多信息，请访问www.merck.com，并通过X（以前的Twitter）、Facebook、Instagram、YouTube和LinkedIn与我们联系。。

Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA

美国新泽西州拉赫韦默克公司的前瞻性声明

This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties.

美国新泽西州拉赫韦市默克公司（以下简称“公司”）的本新闻稿包括1995年《美国私人证券诉讼改革法案》安全港条款所指的“前瞻性声明”。这些声明基于公司管理层当前的信念和期望，并且存在重大风险和不确定性。

There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements..

对于管道候选人，不能保证候选人将获得必要的监管批准，或者证明他们在商业上取得了成功。如果基础假设不准确或风险或不确定性具体化，实际结果可能与前瞻性声明中规定的结果存在重大差异。。

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovation products; and the exposure to litigation, including patent litigation, and/or regulatory actions..

风险和不确定性包括但不限于一般行业条件和竞争；一般经济因素，包括利率和货币汇率波动；美国和国际上制药行业法规和医疗保健立法的影响；医疗保健成本控制的全球趋势；竞争对手取得的技术进步、新产品和专利；新产品开发固有的挑战，包括获得监管部门的批准；公司准确预测未来市场状况的能力；制造困难或延误；国际经济金融不稳定和主权风险；依赖公司专利和其他创新产品保护的有效性；以及诉讼风险，包括专利诉讼和/或监管行动。。

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2023 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov)..

公司没有义务公开更新任何前瞻性声明，无论是由于新信息、未来事件还是其他原因。可能导致结果与前瞻性声明中描述的结果产生重大差异的其他因素可以在公司截至2023年12月31日的10-K表年度报告以及公司向证券交易委员会（SEC）提交的其他文件中找到，这些文件可在SEC的互联网网站（www.SEC.gov）上找到。。