RAHWAY, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that the European Commission (EC) has approved KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, in combination with Padcev (enfortumab vedotin-ejfv), an antibody-drug conjugate, for the first-line treatment of unresectable or metastatic urothelial carcinoma in adults.

新泽西州拉赫韦（商业新闻短讯）--默克（纽约证券交易所：MRK），在美国和加拿大以外被称为MSD，今天宣布，欧盟委员会（EC）已批准默克公司的抗PD-1疗法KEYTRUDA®（pembrolizumab）与抗体-药物偶联物Padcev（enfortumab vedotin ejfv）联合用于成人不可切除或转移性尿路上皮癌的一线治疗。

The decision follows the adoption of the European Society for Medical Oncology and European Association of Urology clinical guidelines recommending the combination as the preferred first-line treatment for these patients, regardless of platinum eligibility..

该决定是在欧洲肿瘤内科学会和欧洲泌尿外科协会临床指南通过后做出的，该指南建议将联合用药作为这些患者的首选一线治疗，无论铂类药物是否合格。。

This approval by the EC also follows the positive recommendation from the Committee for Medicinal Products for Human Use received in July 2024, which was based on results from the first interim analysis of the Phase 3 KEYNOTE-A39 trial (also known as EV-302), which was conducted in a research collaboration with Pfizer (previously Seagen) and Astellas.

欧盟委员会的这一批准还遵循了2024年7月收到的人类使用药品委员会的积极建议，该建议是基于与辉瑞（以前的Seagen）和阿斯特拉斯（Astellas）合作进行的第三阶段KEYNOTE-A39试验（也称为EV-302）的第一次中期分析结果。

In KEYNOTE-A39, KEYTRUDA plus enfortumab vedotin demonstrated statistically significant and clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS) versus platinum-based chemotherapy (gemcitabine plus cisplatin or carboplatin)..

在KEYNOTE-A39中，与铂类化疗（吉西他滨加顺铂或卡铂）相比，KEYTRUDA加enfortumab vedotin在总生存期（OS）和无进展生存期（PFS）方面表现出统计学上显着且具有临床意义的改善。。

At a median follow-up of 17.3 months (range, 0.3 to 37.2 months), the KEYTRUDA plus enfortumab vedotin combination reduced the risk of death by 53% (HR=0.47 [95% CI, 0.38-0.58]; p<0.00001) versus platinum-based chemotherapy (with 133/442 [30%] vs. 226/444 [51%] events observed, respectively), with the combination also reducing the risk of disease progression or death by 55% (HR=0.45 [95% CI, 0.38-0.54]; p<0.00001) versus platinum-based chemotherapy (with 223/442 [50%] vs.

在中位随访17.3个月（范围0.3至37.2个月）时，KEYTRUDA加enfortumab vedotin联合用药与铂类化疗相比，死亡风险降低了53%（HR=0.47[95%CI，0.38-0.58]；p<0.00001）（分别观察到133/442[30%]和226/444[51%]），与铂类化疗相比，联合用药还将疾病进展或死亡风险降低了55%（HR=0.45[95%CI，0.38-0.54]；p<0.00001）（223/442（50%）vs。

307/444 [69%] events observed, respectively)..

分别观察到307/444（69%）个事件）。。

“For the first time in decades, adult patients with unresectable or metastatic urothelial carcinoma have the option of a potential new first-line standard of care that may help extend their lives,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories.

默克研究实验室全球临床开发高级副总裁兼肿瘤学负责人马乔里·格林博士说：“几十年来，无法切除或转移性尿路上皮癌的成年患者首次可以选择可能有助于延长其寿命的潜在新的一线护理标准。”。

“We are pleased with the European Commission’s decision, and we look forward to being able to provide KEYTRUDA as part of this novel treatment regimen for this devastating disease to patients in the European Union.”.

“我们对欧盟委员会的决定感到高兴，我们期待着能够为欧盟患者提供KEYTRUDA作为这种新型治疗方案的一部分。”。

This approval allows marketing of KEYTRUDA in combination with enfortumab vedotin for this indication in all 27 European Union (EU) member states, as well as Iceland, Liechtenstein, Norway and Northern Ireland. KEYTRUDA is now approved for three indications in bladder cancer, and for 28 indications overall in the EU.

该批准允许KEYTRUDA与enfortumab vedotin联合在所有27个欧盟（EU）成员国以及冰岛、列支敦士登、挪威和北爱尔兰销售该适应症。KEYTRUDA现在被批准用于膀胱癌的三种适应症，并且在欧盟总共有28种适应症。

KEYTRUDA was previously approved in the EU as monotherapy for the treatment of locally advanced or metastatic urothelial carcinoma in adults who have received prior platinum-containing chemotherapy, as well as adults who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 with a combined positive score (CPS) ≥10, based on results from KEYNOTE-045 and KEYNOTE-052, respectively.

KEYTRUDA先前在欧盟被批准为单一疗法，用于治疗先前接受过含铂化疗的成年人的局部晚期或转移性尿路上皮癌，以及不符合含顺铂化疗条件且肿瘤表达PD-L1的成年人。根据KEYNOTE-045和KEYNOTE-052的结果，综合阳性评分（CPS）≥10。

In December 2023, KEYTRUDA in combination with enfortumab vedotin was approved in the U.S. for the treatment of adult patients with locally advanced or metastatic urothelial cancer..

2023年12月，KEYTRUDA联合enfortumab vedotin在美国被批准用于治疗局部晚期或转移性尿路上皮癌的成年患者。。

Merck, in collaboration with Pfizer and Astellas, is evaluating this combination as part of an extensive clinical development program in multiple stages of urothelial cancer, including two Phase 3 clinical trials in muscle-invasive bladder cancer in KEYNOTE-B15 (NCT04700124, also known as EV-304) and KEYNOTE-905 (NCT03924895, also known as EV-303)..

默克公司（Merck）与辉瑞（Pfizer）和阿斯特拉斯（Astellas）合作，正在评估这种组合，作为尿路上皮癌多个阶段广泛临床开发计划的一部分，包括KEYNOTE-B15（NCT04700124，也称为EV-304）和KEYNOTE-905（NCT03924895，也称为EV-303）中肌肉浸润性膀胱癌的两项3期临床试验。。

About KEYNOTE-A39

关于KEYNOTE-A39

The KEYNOTE-A39 trial is an open-label, multicenter, randomized, active-controlled Phase 3 trial (ClinicalTrials.gov, NCT04223856) evaluating KEYTRUDA plus enfortumab vedotin compared to platinum-based chemotherapy (gemcitabine plus cisplatin or carboplatin) for the treatment of patients with unresectable or metastatic urothelial carcinoma.

KEYNOTE-A39试验是一项开放标签，多中心，随机，主动对照的3期临床试验（ClinicalTrials.gov，NCT04223856），评估KEYTRUDA加enfortumab vedotin与铂类化疗（吉西他滨加顺铂或卡铂）相比用于治疗不可切除或转移性尿路上皮癌患者。

The primary efficacy outcome measures were PFS as assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and OS. Secondary outcome measures included objective response rate (ORR) and duration of response (DOR) as assessed by BICR according to RECIST v1.1.

主要疗效指标是根据实体瘤反应评估标准（RECIST）v1.1和OS，通过盲法独立中央评估（BICR）评估的PFS。次要结局指标包括根据RECIST v1.1由BICR评估的客观缓解率（ORR）和缓解持续时间（DOR）。

The study enrolled 886 patients who were randomized (1:1) to one of the following treatment arms; all study medications were administered via intravenous infusion:.

该研究招募了886名患者，他们被随机（1:1）分配到以下治疗组之一；所有研究药物均通过静脉输注给药：。

KEYTRUDA 200 mg over 30 minutes on Day 1 and enfortumab vedotin 1.25 mg/kg on Days 1 and 8 of each 21-day cycle.

在每个21天周期的第1天和第8天，在30分钟内服用200毫克KEYTRUDA，服用1.25毫克/千克enfortumab vedotin。

Gemcitabine 1000 mg/m2 on Days 1 and 8 and investigator’s choice of cisplatin 70 mg/m2 or carboplatin (AUC 4.5 or 5 mg/mL/min according to local guidelines) on Day 1 of each 21-day cycle.

吉西他滨1000 mg/m2在第1天和第8天，研究者在每个21天周期的第1天选择顺铂70 mg/m2或卡铂（AUC 4.5或5 mg/mL/min，根据当地指南）。

Treatment with KEYTRUDA and enfortumab vedotin continued until RECIST v1.1-defined progression of disease, unacceptable toxicity or, for KEYTRUDA, a maximum of 35 cycles (up to approximately two years). Assessment of tumor status was performed every nine weeks for 18 months and then every 12 weeks thereafter..

KEYTRUDA和enfortumab vedotin的治疗持续到RECIST v1.1定义的疾病进展，不可接受的毒性，或者对于KEYTRUDA，最多35个周期（最多约两年）。肿瘤状态的评估每9周进行一次，持续18个月，然后每12周进行一次。。

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是一种抗程序性死亡受体-1（PD-1）疗法，它通过提高人体免疫系统的能力来帮助检测和对抗肿瘤细胞。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。KEYTRUDA临床计划旨在了解KEYTRUDA在癌症中的作用以及可能预测患者从KEYTRUDA治疗中受益的可能性的因素，包括探索几种不同的生物标志物。。

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

美国选定的KEYTRUDA®（pembrolizumab）适应症。

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。。

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，可以发生在任何器官系统或组织中，可以同时影响多个身体系统，并且可以在开始治疗后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）的患者永久停用KEYTRUDA，0.9%（26）的患者停用KEYTRUDA。所有被扣留的患者在症状改善后重新启动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.

接受KEYTRUDA作为单一药物治疗的成年cHL患者中有8%（31/389）发生肺炎，其中2.3%的患者发生3-4级肺炎。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..

肺炎导致5.4%（21）的患者停用KEYTRUDA。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%的患者中断了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..

所有被扣留的患者在症状改善后重新启动KEYTRUDA；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。所有被扣留的患者在症状改善后重新启动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，畏光或视野缺损。垂体炎可引起垂体功能减退。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替代甲状腺激素。

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）的患者永久停用KEYTRUDA，0.1%（3）的患者停用KEYTRUDA。

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

所有被扣留的患者在症状改善后重新启动KEYTRUDA；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渗出性皮疹。

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。这些反应导致0.1%（2）的患者永久停药，0.6%（16）的患者停止使用KEYTRUDA。

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

所有被扣留的患者在症状改善后重新启动KEYTRUDA；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。监测输液相关反应的体征和症状。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。密切跟踪患者以获得这些并发症的证据，并及时干预。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。在对照试验之外，不建议使用抗PD-1/PD-L1联合治疗这些患者。

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给药后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%).

在KEYNOTE-189中，当KEYTRUDA在转移性非鳞状细胞癌中接受培美曲塞和铂类化疗时，405名患者中有20%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（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%因不良反应而停用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%），心肌梗死（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.

在KEYNOTE-A18中，当KEYTRUDA对FIGO 2014 III-IVA期宫颈癌患者进行CRT（顺铂加外照射放射治疗[EBRT]，然后进行近距离放射治疗[BT]）时，292例患者中有1.4%发生致命不良反应，其中大肠穿孔，尿路败血症，败血症和阴道出血各1例（0.3%）。

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例急性心肌梗塞，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%).

由于不良反应，15%的患者停用了KEYTRUDA。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.

在KEYNOTE-017和KEYNOTE-913中，MCC患者（n=105）发生的不良反应通常与接受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。

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-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患者（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）。。

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（n=778）进行辅助治疗时，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塞。

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产生严重的不良反应，因此建议女性在治疗期间和最后一次服用后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。在65岁或以上的患者和年轻患者之间，没有观察到安全性或有效性的总体差异。

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。75岁以下患者的致命不良反应发生率为4%，75岁以上患者的致命不良反应发生率为7%。。

Additional Selected KEYTRUDA Indications in the U.S.

美国其他选定的KEYTRUDA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:

KEYTRUDA作为单一药物，适用于通过FDA批准的测试确定的表达PD-L1[肿瘤比例评分（TPS）≥1%]的NSCLC患者的一线治疗，无EGFR或ALK基因组肿瘤畸变，并且是：

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。

Head and Neck Squamous Cell Cancer

头颈部鳞状细胞癌

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作为单一药物，适用于转移性或不可切除的复发性HNSCC患者的一线治疗，其肿瘤表达PD-L1[综合阳性评分（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 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适用于治疗复发或难治性经典霍奇金淋巴瘤（cHL）的成年患者。

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。

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（GEJ）腺癌的成人的一线治疗，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。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, 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。

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。

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。

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 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, 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..

KEYTRUDA适用于治疗成人和儿科不可切除或转移性肿瘤突变负荷高（TMB-H）[≥10突变/兆碱基（mut/Mb）]实体瘤患者，由FDA批准的测试确定，这些患者在先前的治疗后取得了进展，并且没有令人满意的替代治疗选择。。

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。。

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。

About bladder and urothelial carcinoma

关于膀胱癌和尿路上皮癌

Urothelial carcinoma, a type of bladder cancer, begins in the urothelial cells, which line the urethra, bladder, ureters, renal pelvis and some other organs. Globally, it is estimated that approximately 614,300 new cases of bladder cancer are reported annually. In Europe, it is estimated there were approximately 166,000 new cases of bladder cancer diagnosed in 2022, and in the U.S., it is estimated that approximately 83,200 people will be diagnosed with bladder cancer in 2024.

尿路上皮癌是一种膀胱癌，始于尿道、膀胱、输尿管、肾盂和其他一些器官的尿路上皮细胞。据估计，在全球范围内，每年约有614300例膀胱癌新病例报告。在欧洲，估计2022年约有166000例新诊断的膀胱癌病例，在美国，估计2024年约有83200人被诊断患有膀胱癌。

Of those patients diagnosed in the U.S., approximately 12% of cases are locally advanced or metastatic urothelial carcinoma at diagnosis, and many patients who are diagnosed at an advanced stage face a poor prognosis..

在美国诊断的那些患者中，大约12%的病例在诊断时是局部晚期或转移性尿路上皮癌，许多被诊断为晚期的患者预后不良。。

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。Padcev®和Padcev设备是Agensys，Inc.和Seagen Inc.共同拥有的商标。

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。。

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 http://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http://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.

我们立志成为世界上领先的研究密集型生物制药公司，今天，我们处于研究的前沿，以提供创新的健康解决方案，促进人类和动物疾病的预防和治疗。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 X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn..

欲了解更多信息，请访问www.merck.com并与us X（前Twitter）、Facebook、Instagram、YouTube和LinkedIn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。。

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.