May 31, 2025 8:00 am ET

2025年5月31日 上午8:00（美国东部时间）

First pivotal Phase 3 trial to show superiority of KEYTRUDA plus a TROP2 antibody-drug conjugate, Trodelvy, versus standard of care in first-line metastatic TNBC

首个关键的三期试验显示，KEYTRUDA联合TROP2抗体药物偶联物Trodelvy在一线转移性三阴性乳腺癌中优于标准治疗。

RAHWAY, N.J.--(BUSINESS WIRE)--

新泽西州拉威市--（商业资讯）--

Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that KEYTRUDA

默克公司（纽约证券交易所代码：MRK），在美国和加拿大以外地区称为MSD，今天宣布了KEYTRUDA的消息。

®

®

(pembrolizumab) plus Trodelvy

(pembrolizumab) 加 Trodelvy

®

®

(sacituzumab govitecan-hziy) reduced the risk of disease progression or death by 35% (HR=0.65, p<0.001) versus KEYTRUDA plus chemotherapy for the first-line treatment of patients with PD-L1+ (Combined Positive Score [CPS] ≥10) inoperable (unresectable) locally advanced or metastatic triple-negative breast cancer (TNBC), as determined by an FDA-approved test.

（sacituzumab govitecan-hziy）与KEYTRUDA联合化疗相比，在PD-L1+（综合阳性评分[CPS]≥10）不可手术（无法切除）的局部晚期或转移性三阴性乳腺癌（TNBC）的一线治疗中，根据FDA批准的检测方法，可将疾病进展或死亡的风险降低35%（HR=0.65，p<0.001）。

KEYTRUDA, when given in combination with Gilead’s TROP2 antibody-drug conjugate (ADC) Trodelvy, resulted in a median progression-free survival (PFS) of 11.2 months versus 7.8 months when KEYTRUDA was given in combination with chemotherapy. These data from the pivotal Phase 3 ASCENT-04/KEYNOTE-D19 study will be presented today as a late-breaking oral presentation at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #LBA109) and were selected for the official ASCO Press Program..

KEYTRUDA与Gilead的TROP2抗体药物偶联物（ADC）Trodelvy联合使用时，中位无进展生存期（PFS）达到11.2个月，而KEYTRUDA与化疗联合使用时为7.8个月。这些来自关键的III期ASCENT-04/KEYNOTE-D19研究的数据将于今天在2025年美国临床肿瘤学会（ASCO）年会上作为最新口头报告展示（摘要编号#LBA109），并被选入ASCO官方新闻计划。

“These results have the potential to be an important advancement for patients with PD-L1–positive metastatic triple-negative breast cancer, a population for whom first-line options remain limited,” said Sara Tolaney, MD, MPH, Dana-Farber Cancer Institute and primary investigator of the ASCENT-04/KEYNOTE-D19 study.

“这些结果有潜力成为PD-L1阳性转移性三阴性乳腺癌患者的重要进展，这一群体的一线治疗选择仍然有限，”达纳-法伯癌症研究所的莎拉·托拉内医学博士、公共卫生硕士，以及ASCENT-04/KEYNOTE-D19研究的主要研究者表示。

“By combining sacituzumab govitecan with pembrolizumab, we’re seeing meaningful gains in progression-free survival and a promising trend in overall survival—findings that could support a new frontline standard of care for this aggressive disease.”.

“通过将萨西图珠单抗戈维替康与派姆单抗联合使用，我们在无进展生存期方面看到了显著的提升，并且在总生存期方面也呈现出有希望的趋势——这些发现可能为这种侵袭性疾病提供一个新的前线治疗标准。”

The safety profile of KEYTRUDA plus Trodelvy in this study was consistent with the known safety profile of each agent. No new safety signals were identified with the combination. The two companies plan to share these results with regulatory authorities worldwide.

本研究中，KEYTRUDA联合Trodelvy的安全性与每种药物已知的安全性一致。联合用药未发现新的安全性信号。两家公司计划将这些结果分享给全球的监管机构。

“We’re committed to building on the established role of KEYTRUDA as a foundational treatment for people with TNBC to provide new options in earlier lines of treatment, in the hope of improving outcomes for people living with this disease,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories.

“我们致力于在KEYTRUDA作为TNBC患者基础治疗的既定作用之上，提供早期治疗的新选择，希望改善患有这种疾病的患者的预后，”默克研究实验室高级副总裁兼肿瘤学全球临床开发主管Marjorie Green博士说道。

“These data support the addition of this TROP2-directed ADC to KEYTRUDA, demonstrating the potential to help people with TNBC and to give doctors another option to treat this disease.”.

“这些数据支持将这种靶向TROP2的ADC与KEYTRUDA联合使用，证明了其帮助三阴性乳腺癌（TNBC）患者的潜力，并为医生提供了另一种治疗该疾病的选择。”

A statistically significant and clinically meaningful improvement was observed with KEYTRUDA plus Trodelvy (n=221), showing a 35% reduction in the risk of disease progression or death (HR=0.65; p<0.001) in the intent-to-treat population compared to KEYTRUDA plus chemotherapy (n=222). The PFS benefit was generally consistent across key prespecified subgroups including age, curative treatment-free interval and geographic region..

在KEYTRUDA联合Trodelvy（n=221）治疗组中观察到统计学显著且临床意义重大的改善，与KEYTRUDA联合化疗（n=222）相比，意向治疗人群的疾病进展或死亡风险降低了35%（HR=0.65；p<0.001）。无进展生存期（PFS）的获益在关键预设亚组中总体一致，包括年龄、无治愈性治疗间隔和地理区域。

A higher objective response rate (ORR) was observed for the KEYTRUDA plus Trodelvy combination (59.7% [95% CI, 52.9-66.3] versus 53.2% [95% CI, 46.4-59.9]), including 13% and 8% with a complete response, respectively, in the KEYTRUDA plus Trodelvy and KEYTRUDA plus chemotherapy arms. Notably, a substantially longer duration of response (DOR) was observed with KEYTRUDA plus Trodelvy (16.5 months [95% CI, 12.7-19.5] versus 9.2 months [95% CI, 7.6-11.3]).

观察到KEYTRUDA联合Trodelvy的客观缓解率（ORR）更高（59.7% [95% CI, 52.9-66.3] 对比 53.2% [95% CI, 46.4-59.9]），其中在KEYTRUDA联合Trodelvy组和KEYTRUDA联合化疗组中分别有13%和8%的患者达到完全缓解。值得注意的是，KEYTRUDA联合Trodelvy的缓解持续时间（DOR）显著更长（16.5个月 [95% CI, 12.7-19.5] 对比 9.2个月 [95% CI, 7.6-11.3]）。

Encouraging trends in overall survival (OS) were also observed, but data are immature at the time of PFS primary analysis. Overall survival follow-up remains ongoing and will continue to be monitored as a key secondary endpoint..

同时也观察到总生存期（OS）有鼓舞人心的趋势，但在PFS主要分析时数据尚不成熟。总生存期的随访仍在进行中，并将继续作为关键次要终点进行监测。

Merck has a comprehensive clinical development program in various subtypes of breast cancer including evaluating KEYTRUDA in combination with investigational TROP2 ADCs (trophoblast cell-surface antigen-directed antibody-drug conjugates) in metastatic and early-stage cancers. The company has four ongoing Phase 3 studies in breast cancer, with two being in metastatic disease..

默克公司在乳腺癌的各种亚型中开展了全面的临床开发计划，包括在转移性和早期癌症中评估KEYTRUDA与实验性TROP2 ADC（滋养层细胞表面抗原导向的抗体药物偶联物）的联合应用。该公司在乳腺癌领域正在进行四项III期研究，其中两项针对转移性疾病。

In the U.S. and Europe, KEYTRUDA has two approved indications in TNBC: for the treatment of patients with high-risk early-stage TNBC in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery; and in combination with chemotherapy 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..

在美国和欧洲，KEYTRUDA在三阴性乳腺癌（TNBC）中有两个已批准的适应症：用于高危早期三阴性乳腺癌患者，与化疗联合作为新辅助治疗，然后在手术后继续作为单一药物的辅助治疗；以及与化疗联合使用，用于治疗局部复发不可切除或转移性三阴性乳腺癌患者，其肿瘤表达PD-L1（CPS≥10），并由FDA批准的测试确定。

As

正如

announced

宣布

, data spanning more than 25 types of cancer are being presented from Merck’s broad oncology portfolio and investigational pipeline at the 2025 ASCO Annual Meeting.

，涵盖超过25种癌症类型的数据正在2025年ASCO年会上从默克广泛的肿瘤学产品组合和研究管线中展示。

About the ASCENT-04/KEYNOTE-D19 Study

关于ASCENT-04/KEYNOTE-D19研究

In 2021, Merck entered a collaboration with Gilead to investigate KEYTRUDA plus Trodelvy in the Phase 3 ASCENT-04/KEYNOTE-D19 open-label, global trial (ClinicalTrials.gov,

2021年，默克与吉利德达成合作，在开放标签的全球三期ASCENT-04/KEYNOTE-D19试验中（ClinicalTrials.gov），研究KEYTRUDA联合Trodelvy的效果。

NCT05382286

NCT05382286

). The primary endpoint is PFS as determined by BICR using RECIST v1.1. Secondary endpoints include OS, ORR, DOR, time to onset of response (TTR), patient-reported outcomes (PROs) and safety. The study enrolled 443 patients who were randomized in a 1:1 ratio to receive either sacituzumab govitecan (10 mg/kg intravenously [IV] on Days 1 and 8 of a 21-day cycle) plus pembrolizumab (200 mg IV on Day 1 of a 21-day cycle) or chemotherapy plus pembrolizumab.

）。主要终点是由BICR根据RECIST v1.1评估的PFS。次要终点包括OS、ORR、DOR、反应起效时间（TTR）、患者报告结果（PROs）和安全性。研究共纳入443例患者，按1:1比例随机分配接受戈沙妥珠单抗（10 mg/kg静脉注射[IV]，21天周期的第1天和第8天给药）联合帕博利珠单抗（200 mg IV，21天周期的第1天给药），或化疗联合帕博利珠单抗治疗。

The chemotherapy regimen included gemcitabine plus carboplatin, paclitaxel, or nab-paclitaxel. Treatment continued until blinded independent central review (BICR)-verified disease progression or unacceptable toxicity and at this time patients randomized to chemotherapy were allowed to crossover and receive sacituzumab govitecan upon disease progression..

化疗方案包括吉西他滨联合卡铂、紫杉醇或多西他赛。治疗持续至盲态独立中心审查（BICR）确认的疾病进展或不可接受的毒性，在此情况下，随机分配至化疗组的患者在疾病进展时被允许交叉并接受戈沙妥珠单抗治疗。

About triple-negative breast cancer (TNBC)

关于三阴性乳腺癌（TNBC）

Triple-negative breast cancer is the most aggressive type of breast cancer, which has the highest risk of recurrence within the first five years after diagnosis and is associated with worse outcomes compared to other forms of breast cancer. Approximately 10-15% of patients with breast cancer are diagnosed with TNBC.

三阴性乳腺癌是乳腺癌中最具侵袭性的类型，在诊断后的头五年内复发风险最高，且与其他类型的乳腺癌相比预后较差。大约10-15%的乳腺癌患者被诊断为三阴性乳腺癌。

While some breast cancers may test positive for estrogen receptors, progesterone receptors or overexpression of human epidermal growth factor receptor 2 (HER2), TNBC tests negative for all three. Triple-negative breast cancer tends to be more common in people who are younger than 40 years of age, who are Black or who have a .

虽然某些乳腺癌可能检测出雌激素受体、孕激素受体或人类表皮生长因子受体2（HER2）过度表达呈阳性，但三阴性乳腺癌对这三种检测均呈阴性。三阴性乳腺癌在40岁以下、黑人或有特定基因突变的人群中更为常见。

BRCA

乳腺癌易感基因 (BRCA)

1 mutation.

1 次变异。

About Merck’s research in women’s cancers

关于默克在女性癌症方面的研究

Merck is advancing research aimed at expanding treatment options for certain breast and gynecologic (ovarian, cervical and endometrial) cancers, with a goal of improving outcomes for more patients affected by these diseases. Breast cancer and gynecological cancers are the first and second most commonly occurring cancer types among women worldwide, respectively, and Merck aims to give patients facing these devastating diseases options.

默克公司正在推进旨在扩大某些乳腺癌和妇科（卵巢、宫颈和子宫内膜）癌症治疗选择的研究，目标是改善更多受这些疾病影响的患者的治疗效果。乳腺癌和妇科癌症分别是全球女性中最常见和第二常见的癌症类型，默克公司旨在为面临这些毁灭性疾病困扰的患者提供更多的治疗选择。

With more than 20 clinical trials in more than 18,000 patients around the world, Merck is driving innovative research to purposefully advance standards of care in women’s cancers. Merck’s research efforts include trials focused on evaluating its medicines in earlier stages, as well as identifying novel mechanisms and new combinations with these treatments.

默克公司在全球范围内开展了20多项临床试验，涉及18,000多名患者，致力于推动创新研究，以有目的地提升女性癌症的护理标准。默克的研究工作包括评估其药物在更早期阶段的效果，同时探索新的作用机制及这些治疗方法的新组合。

Merck is working to develop a portfolio and pipeline to address the impact of women’s cancers on patients, their families and communities globally..

默克正致力于开发一个项目组合和管道，以应对女性癌症对全球患者、她们的家庭和社区的影响。

About KEYTRUDA

关于KEYTRUDA

®

®

(pembrolizumab) injection, 100 mg

（派姆单抗）注射剂，100毫克

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，通过增强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与其配体PD-L1和PD-L2之间的相互作用，从而激活T淋巴细胞，这可能对肿瘤细胞和健康细胞均产生影响。

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..

默克公司拥有行业内最大的免疫肿瘤临床研究项目。目前，有超过1600项试验正在研究KEYTRUDA在各种癌症和治疗环境中的应用。KEYTRUDA临床项目旨在了解KEYTRUDA在不同癌症中的作用，以及可能预测患者从KEYTRUDA治疗中获益可能性的因素，包括探索几种不同的生物标志物。

Selected KEYTRUDA

选定的KEYTRUDA

®

®

(pembrolizumab) Indications in the U.S.

（派姆单抗）在美国的适应症

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 适用于高风险早期三阴性乳腺癌 (TNBC) 患者的治疗，与化疗联合作为新辅助治疗，然后在手术后继续作为单一药物进行辅助治疗。

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联合化疗适用于治疗局部复发性不可切除或转移性三阴性乳腺癌（TNBC）患者，其肿瘤表达PD-L1（CPS≥10），需通过FDA批准的检测方法确定。

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

在美国，有关选定的重要安全信息之后，查看KEYTRUDA的其他选定适应症。

Selected Important Safety Information for KEYTRUDA

KEYTRUDA精选重要安全信息

Severe and Fatal Immune-Mediated Adverse Reactions

严重和致命的免疫介导不良反应

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，属于一类结合程序性死亡受体-1（PD-1）或程序性死亡配体1（PD-L1）的药物，通过阻断PD-1/PD-L1通路，解除对免疫反应的抑制，可能打破外周耐受并引发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发生在任何器官系统或组织，可能同时影响多个身体系统，并且可能在开始治疗后的任何时间或停止治疗后发生，这些反应可能严重甚至致命。此处列出的重要免疫介导不良反应可能未包含所有可能的严重和致命免疫介导不良反应。

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.

密切监测患者可能出现的作为潜在免疫介导不良反应临床表现的症状和体征。早期识别和管理对于确保抗PD-1/PD-L1治疗的安全使用至关重要。在基线时评估肝酶、肌酐和甲状腺功能，并在治疗期间定期监测。

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使用KEYTRUDA的三阴性乳腺癌（TNBC）患者，应在基线、手术前以及临床需要时监测血液皮质醇水平。如果怀疑发生免疫介导的不良反应，应启动适当的检查以排除其他可能的原因，包括感染。及时开始医学管理，必要时进行专科会诊。

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，暂停或永久停止使用KEYTRUDA。一般情况下，如果需要中断或停止使用KEYTRUDA，应给予系统性皮质类固醇治疗（每天1至2毫克/千克的泼尼松或等效药物），直到症状改善至1级或更低。一旦改善至1级或更低，开始逐渐减少皮质类固醇剂量，并在至少1个月内持续减量。

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

考虑对那些用皮质类固醇治疗不能控制不良反应的患者给予其他系统性免疫抑制剂。

Immune-Mediated Pneumonitis

免疫介导的肺炎

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可能引起免疫介导的肺炎。既往接受过胸部放疗的患者发生率较高。在使用KEYTRUDA治疗的患者中，有3.4%（94/2799）发生了免疫介导的肺炎，其中包括致命性（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) 的患者需要使用全身性皮质类固醇。肺炎导致 1.3% (36) 的患者永久停用 KEYTRUDA，0.9% (26) 的患者暂停用药。所有暂停用药的患者在症状改善后重新开始使用 KEYTRUDA；其中 23% 的患者出现复发。94 名患者中 59% 的肺炎症状得到解决。

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.

在接受KEYTRUDA单药治疗的成人cHL患者中，8%（31/389）发生了肺炎，其中2.3%的患者为3-4级。患者接受高剂量皮质类固醇治疗的中位持续时间为10天（范围：2天至53个月）。有或无既往胸部放疗史的患者的肺炎发生率相似。

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名）患者停止使用KEYTRUDA。在发生肺炎的患者中，42%中断了KEYTRUDA治疗，68%停止了KEYTRUDA治疗，77%的患者病情得到缓解。

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).

在接受KEYTRUDA单药作为NSCLC辅助治疗的580例切除NSCLC成年患者中，7%（41/580）发生肺炎，包括致命性（0.2%）、4级（0.3%）和3级（1%）的不良反应。患者接受高剂量皮质类固醇治疗的中位持续时间为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%）患者停止使用KEYTRUDA。在发生肺炎的患者中，54%中断了KEYTRUDA治疗，63%停止了KEYTRUDA治疗，71%得到了缓解。

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，可能表现为腹泻。在接受皮质类固醇治疗后仍无改善的免疫介导性结肠炎患者中，已有巨细胞病毒感染/再活化的报告。对于皮质类固醇难治性结肠炎的病例，考虑重复感染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，其中包括4级（<0.1%）、3级（1.1%）和2级（0.4%）反应。69%（33/48）的患者需要使用全身性皮质类固醇；4.2%的患者需要额外的免疫抑制治疗。结肠炎导致0.5%（15）的患者永久停用KEYTRUDA，0.5%（13）的患者暂停用药。

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

所有患者在症状改善后重新开始使用KEYTRUDA；其中，23%的患者出现复发。在48名患者中，85%的患者结肠炎得到解决。

Hepatotoxicity and Immune-Mediated Hepatitis

肝毒性和免疫介导的肝炎

KEYTRUDA as a Single Agent

KEYTRUDA单药治疗

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可能引起免疫介导的肝炎。在接受KEYTRUDA治疗的患者中，有0.7%（19/2799）发生免疫介导的肝炎，其中包括4级（<0.1%）、3级（0.4%）和2级（0.1%）反应。68%（13/19）的患者需要全身性皮质类固醇治疗；11%的患者需要额外的免疫抑制治疗。

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名）患者永久停用KEYTRUDA，0.3%（9名）患者暂停用药。所有暂停用药的患者在症状改善后重新开始使用KEYTRUDA；其中无人复发。在19名患者中，79%的肝炎得到解决。

KEYTRUDA With Axitinib

KEYTRUDA联合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与阿昔替尼联合使用可能会导致肝脏毒性。在开始治疗前和治疗期间定期监测肝酶。与单独用药相比，考虑更频繁地进行监测。如果肝酶升高，应中断KEYTRUDA和阿昔替尼的使用，并根据需要考虑使用皮质类固醇。

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.

通过KEYTRUDA与阿昔替尼联合使用，与单独使用KEYTRUDA相比，3级和4级丙氨酸氨基转移酶（ALT）升高（20%）和天门冬氨酸氨基转移酶（AST）升高（13%）的发生频率更高。其中59%的ALT升高患者接受了全身性皮质类固醇治疗。

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.

在ALT ≥3倍正常上限（ULN）（2-4级，n=116）的患者中，94%的患者ALT降至0-1级。在重新使用KEYTRUDA（n=3）或阿昔替尼（n=34）单药治疗或两者联合治疗（n=55）的92名患者中，观察到1名接受KEYTRUDA的患者、16名接受阿昔替尼的患者和24名接受两者联合治疗的患者再次出现ALT ≥3倍ULN的情况。

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

所有ALT ≥3 ULN复发的患者随后都从事件中恢复。

Immune-Mediated Endocrinopathies

免疫介导的内分泌疾病

Adrenal Insufficiency

肾上腺功能不全

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 可能导致原发性或继发性肾上腺功能不全。对于 2 级或更高级别的症状，应根据临床指征启动对症治疗，包括激素替代疗法。根据严重程度暂停使用 KEYTRUDA。在使用 KEYTRUDA 的患者中，0.8%（22/2799）出现肾上腺功能不全，其中包括 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) 的患者需要使用全身性皮质类固醇；其中大多数患者仍继续使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) 的患者暂停用药。所有暂停用药的患者在症状改善后重新开始使用 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 可能导致免疫介导的垂体炎。垂体炎可能表现为与肿块效应相关的急性症状，例如头痛、畏光或视野缺损。垂体炎可能导致垂体功能减退。根据需要开始激素替代治疗。根据严重程度，暂停或永久停用 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.

垂体炎发生在接受KEYTRUDA治疗的患者中占0.6%（17/2799），其中包括4级（<0.1%）、3级（0.3%）和2级（0.2%）反应。94%（16/17）的患者需要全身性皮质类固醇治疗；其中大多数患者继续使用全身性皮质类固醇。垂体炎导致0.1%（4名）患者永久停用KEYTRUDA，0.3%（7名）患者暂停用药。

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

所有患者在症状改善后重新开始使用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可能引起免疫介导的甲状腺疾病。甲状腺炎可以伴随或不伴随内分泌病出现。甲状腺功能减退可能继发于甲状腺功能亢进。根据临床需要，对甲状腺功能减退开始激素替代治疗，或对甲状腺功能亢进进行药物治疗。根据严重程度，暂停或永久停用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..

甲状腺炎发生在0.6%（16/2799）的接受KEYTRUDA治疗的患者中，包括2级（0.3%）。没有患者因此停药，但有<0.1%（1例）的患者暂停了KEYTRUDA治疗。

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.

在接受KEYTRUDA治疗的患者中，3.4%（96/2799）出现甲状腺功能亢进，其中包括3级（0.1%）和2级（0.8%）。这导致<0.1%（2名）患者永久停用KEYTRUDA，0.3%（7名）患者暂停用药。所有暂停用药的患者在症状改善后重新开始使用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.

在接受KEYTRUDA治疗的患者中，8%（237/2799）出现甲状腺功能减退，其中包括3级（0.1%）和2级（6.2%）。这导致<0.1%（1名）患者永久停用KEYTRUDA，0.5%（14名）患者暂停用药。所有暂停用药的患者在症状改善后重新开始使用KEYTRUDA。大多数甲状腺功能减退的患者需要长期的甲状腺激素替代治疗。

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.

在1185名头颈鳞状细胞癌（HNSCC）患者中，新发或恶化的甲状腺功能减退症发生率较高，16%的患者在使用KEYTRUDA单药治疗或与铂类和氟尿嘧啶（FU）联合治疗时出现此情况，其中包括3级（0.3%）甲状腺功能减退症。在389名经典霍奇金淋巴瘤（cHL）成年患者中，新发或恶化的甲状腺功能减退症发生率更高（17%），这些患者接受KEYTRUDA单药治疗，其中包括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..

在580名切除的非小细胞肺癌（NSCLC）患者中，新发或恶化的甲状腺功能亢进症发生率较高，在接受KEYTRUDA单药作为辅助治疗的患者中占11%，其中包括3级（0.2%）甲状腺功能亢进症。在580名切除的非小细胞肺癌（NSCLC）患者中，新发或恶化的甲状腺功能减退症发生率较高，在接受KEYTRUDA单药作为辅助治疗的患者中占22%（KEYNOTE-091），其中包括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），可表现为糖尿病酮症酸中毒

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.

监测患者是否出现高血糖或糖尿病的其他体征和症状。根据临床指征启动胰岛素治疗。根据严重程度暂停使用KEYTRUDA。在接受KEYTRUDA治疗的患者中，有0.2%（6/2799）发生1型糖尿病。这导致<0.1%（1名）患者永久停药，并在<0.1%（1名）患者中暂停使用KEYTRUDA。

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

所有患者在症状改善后均重新开始使用KEYTRUDA。

Immune-Mediated Nephritis With Renal Dysfunction

免疫介导的肾炎伴肾功能障碍

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可能引起免疫介导的肾炎。在接受KEYTRUDA治疗的患者中，有0.3%（9/2799）发生免疫介导的肾炎，其中包括4级（<0.1%）、3级（0.1%）和2级（0.1%）反应。89%（8/9）的患者需要全身性皮质类固醇治疗。肾炎导致0.1%（3名）患者永久停用KEYTRUDA，并导致0.1%（3名）患者暂停用药。

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

所有患者在症状改善后重新开始使用KEYTRUDA；其中，没有患者出现复发。9名患者中有56%的肾炎得到解决。

Immune-Mediated Dermatologic Adverse Reactions

免疫介导的皮肤病学不良反应

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 可能引发免疫介导的皮疹或皮炎。使用抗 PD-1/PD-L1 治疗时已报告出现剥脱性皮炎，包括史蒂文斯-约翰逊综合征、伴有嗜酸性粒细胞增多及全身症状的药物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至中度非剥脱性皮疹。

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.

根据严重程度暂停或永久停止使用KEYTRUDA。在接受KEYTRUDA治疗的患者中，有1.4%（38/2799）发生了免疫介导的皮肤不良反应，其中包括3级（1%）和2级（0.1%）反应。40%（15/38）的患者需要全身性皮质类固醇治疗。这些反应导致0.1%（2）的患者永久停用KEYTRUDA，0.6%（16）的患者暂停使用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..

所有患者在症状改善后重新开始使用KEYTRUDA；其中6%的患者出现复发。在38名患者中，79%的患者的反应得到解决。

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.

以下临床显著的免疫介导不良反应在接受KEYTRUDA治疗的患者中发生率低于1%（除非另有说明），或在使用其他抗PD-1/PD-L1治疗时被报告。其中一些不良反应已有严重或致命病例报告。

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、重症肌无力综合征/重症肌无力（包括加重）、吉兰-巴雷综合征、神经麻痹、自身免疫性神经病；眼部：葡萄膜炎、虹膜炎和其他眼部炎症毒性可能会发生。

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..

一些病例可能与视网膜脱离有关。包括失明在内的不同程度的视力障碍可能发生。如果葡萄膜炎与其他免疫介导的不良反应同时发生，应考虑伏格特-小柳-原田样综合征，因为这可能需要使用全身性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；肌肉骨骼及结缔组织：肌炎/多发性肌炎、横纹肌溶解（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；血液系统/免疫：溶血性贫血、再生障碍性贫血、噬血细胞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可能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，在接受KEYTRUDA的2799名患者中已有0.2%报告此类反应。监测输液相关反应的体征和症状。对于1级或2级反应，应中断输液或减慢输液速度。

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

对于3级或4级反应，停止输注并永久停用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).

接受抗PD-1/PD-L1治疗之前或之后进行同种异体HSCT的患者可能会发生致命及其他严重并发症。移植相关并发症包括超急性移植物抗宿主病（GVHD）、急性和慢性GVHD、减强度预处理后的肝静脉闭塞性疾病，以及需要使用类固醇的发热综合征（无明确感染原因）。

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..

这些并发症可能在抗 PD-1/PD-L1 治疗与异基因 HSCT 之间的干预治疗后仍然发生。密切监测患者这些并发症的证据，并及时进行干预。在异基因 HSCT 前或后使用抗 PD-1/PD-L1 治疗时，应权衡其益处与风险。

Increased Mortality in Patients With Multiple Myeloma

多发性骨髓瘤患者的死亡率增加

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，将KEYTRUDA加入沙利度胺类似物和地塞米松的治疗方案会增加死亡率。不建议在对照试验之外使用这种联合方案中的抗PD-1/PD-L1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..

基于其作用机制，KEYTRUDA 在给孕妇使用时可能会对胎儿造成伤害。请告知女性这一潜在风险。对于具有生殖潜力的女性，在开始使用 KEYTRUDA 之前应确认妊娠状态，并建议她们在治疗期间及最后一剂后的 4 个月内使用有效避孕措施。

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试验中，555名晚期黑色素瘤患者中有9%因不良反应而停用KEYTRUDA；导致永久停药的不良反应中，超过一例的包括结肠炎（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%）为疲劳（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试验中，当KEYTRUDA作为单药治疗用于III期黑色素瘤患者时，509例患者中有14%因不良反应永久停用KEYTRUDA；最常见的（≥1%）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%发生了严重不良反应。

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研究中，当KEYTRUDA单药用于IIB或IIC期黑色素瘤患者时，这些患者的不良反应与来自KEYNOTE-054研究的1011名III期黑色素瘤患者中观察到的不良反应相似。

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试验中，当KEYTRUDA与培美曲塞和铂类化疗联合用于转移性非鳞状非小细胞肺癌时，405名患者中有20%因不良反应而停用KEYTRUDA。导致永久停用KEYTRUDA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%）包括恶心（56%）、疲劳（56%）、便秘（35%）、腹泻（31%）、食欲减退（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研究中，当KEYTRUDA与卡铂以及紫杉醇或多西他赛联合用于转移性鳞状非小细胞肺癌时，在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为发热性中性粒细胞减少、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..

在KEYNOTE-407中观察到的不良反应与在KEYNOTE-189中观察到的相似，不同之处在于，在KEYNOTE-407中，与安慰剂加化疗组相比，KEYTRUDA加化疗组中脱发（47% 对 36%）和周围神经病变（31% 对 25%）的发生率增加。

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试验中，636名晚期非小细胞肺癌患者中有19%因不良反应而停用KEYTRUDA；最常见的不良反应是肺炎（3%）、不明原因死亡（1.6%）和肺部感染（1.4%）。至少2%的患者报告的最常见的严重不良反应包括肺部感染（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%）为疲劳（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研究中，682名转移性非小细胞肺癌患者中，8%因不良反应停止使用KEYTRUDA单药治疗；最常见的是肺炎（1.8%）。最常见的不良反应（≥20%）为食欲减退（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研究中，可切除的非小细胞肺癌患者接受KEYTRUDA联合含铂化疗（作为新辅助治疗）并继续使用单药辅助治疗时发生的不良反应，总体上与其他临床试验中跨肿瘤类型接受KEYTRUDA联合化疗的患者所出现的不良反应相似。

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联合化疗的患者中最常见的不良反应（报告率≥20%）包括疲劳/虚弱、恶心、便秘、腹泻、食欲减退、皮疹、呕吐、咳嗽、呼吸困难、发热、脱发、周围神经病变、黏膜炎、口腔炎、头痛、体重减轻、腹痛、关节痛、肌肉痛、失眠、手足红肿综合征、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 与含铂化疗联合使用作为新辅助治疗时，396 名患者中有 34% 发生了严重不良反应。最常见的（≥2%）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%)..

发生了1.3%的患者出现致命的不良反应，包括不明原因导致的死亡（0.8%）、败血症（0.3%）和免疫介导的肺部疾病（0.3%）。在使用KEYTRUDA联合含铂化疗的患者中，有18%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用的最常见的不良反应（≥1%）为急性肾损伤（1.8%）、间质性肺病（1.8%）、贫血（1.5%）、中性粒细胞减少（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 的辅助治疗阶段，当 KEYTRUDA 作为单一药物进行辅助治疗时，290 名患者中有 14% 出现了严重不良反应。最常见的严重不良反应是肺炎 (3.4%)。发生了 1 例致命的肺出血不良反应。因不良反应而永久停用 KEYTRUDA 的患者占接受 KEYTRUDA 单药辅助治疗患者的 12%；导致永久停用 KEYTRUDA 的最常见不良反应（≥1%）为腹泻 (1.7%)、间质性肺病 (1.4%)、天冬氨酸氨基转移酶升高 (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.

在KEYNOTE-091中观察到的不良反应总体上与接受KEYTRUDA单药治疗的其他NSCLC患者中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。发生了两例致死性心肌炎的不良反应。

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试验中，300名头颈鳞状细胞癌（HNSCC）患者中有12%因不良事件停止使用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%）为疲劳（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试验中，当KEYTRUDA与铂类（顺铂或卡铂）和氟尿嘧啶（FU）化疗联合使用时，在276名头颈部鳞状细胞癌（HNSCC）患者中，有16%的患者因不良反应而停用KEYTRUDA。导致永久停用KEYTRUDA的最常见不良反应为肺炎（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%）为恶心（51%）、疲劳（49%）、便秘（37%）、呕吐（32%）、黏膜炎（31%）、腹泻（29%）、食欲减退（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试验中，192名头颈部鳞状细胞癌（HNSCC）患者中有17%因不良反应而停用KEYTRUDA。45%的患者发生了严重不良反应。至少2%的患者报告的最常见的严重不良反应包括肺炎、呼吸困难、意识模糊状态、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%）为疲劳、食欲减退和呼吸困难。在头颈部鳞状细胞癌（HNSCC）患者中发生的不良反应通常与接受KEYTRUDA单药治疗的黑色素瘤或非小细胞肺癌（NSCLC）患者中的不良反应相似，但面部水肿和新发或恶化的甲状腺功能减退症的发生率有所增加。

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试验中，148名cHL患者中有14%因不良反应停止使用KEYTRUDA。接受KEYTRUDA的患者中有30%发生严重不良反应；其中≥1%的包括肺炎、肺部感染、发热、心肌炎、急性肾损伤、发热性中性粒细胞减少和败血症。三名患者死于非疾病进展原因：2名患者因异基因造血干细胞移植后并发症死亡，1名患者死因不明。

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%）为上呼吸道感染（41%）、肌肉骨骼疼痛（32%）、腹泻（22%）、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 名 cHL 患者中有 5% 因不良反应停止使用 KEYTRUDA。16% 的患者发生严重不良反应；其中 ≥1% 为肺炎、肺炎、发热、呼吸困难、GVHD 和带状疱疹。两名患者死于非疾病进展原因：1 名患者因后续异基因 HSCT 后出现 GVHD 死亡，另 1 名患者因败血性休克死亡。

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%）为疲劳（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试验中，53名PMBCL患者中有8%因不良反应停止使用KEYTRUDA。26%的患者发生了严重不良反应，其中包括心律失常（4%）、心包填塞（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%）包括肌肉骨骼疼痛（30%）、上呼吸道感染和发热（各28%）、咳嗽（26%）、疲劳（23%）以及呼吸困难（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研究中，当KEYTRUDA与enfortumab vedotin联合用于治疗局部晚期或转移性尿路上皮癌患者（n=440）时，3.9%的患者发生了致死性不良反应，其中包括急性呼吸衰竭（0.7%）、肺炎（0.5%）以及肺炎/间质性肺病（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；其中≥2%患者的严重不良反应包括皮疹（6%）、急性肾损伤（5%）、肺炎/间质性肺病（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% 的患者永久停用了 KEYTRUDA。导致永久停用 KEYTRUDA 的最常见不良反应（≥2%）是肺炎/间质性肺病（4.8%）和皮疹（3.4%）。在使用 KEYTRUDA 联合 enfortumab vedotin 治疗的患者中，最常见的不良反应（≥20%）包括皮疹（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%）、食欲减退（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研究中，370名局部晚期或转移性尿路上皮癌患者中有11%因不良反应而停止使用KEYTRUDA。42%的患者发生了严重不良反应；其中≥2%的包括尿路感染、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%）为疲劳（38%）、肌肉骨骼疼痛（24%）、食欲减退（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试验中，266名局部晚期或转移性尿路上皮癌患者中有8%因不良反应而停用KEYTRUDA。导致永久停用KEYTRUDA的最常见不良反应是肺炎（1.9%）。39%的接受KEYTRUDA治疗的患者发生了严重不良反应；其中≥2%为尿路感染、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治疗的患者中最常见的不良反应（≥20%）为疲劳（38%）、肌肉骨骼疼痛（32%）、瘙痒（23%）、食欲减退（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试验中，148名高危NMIBC患者中有11%因不良反应停止使用KEYTRUDA。导致永久停用KEYTRUDA的最常见不良反应是肺炎（1.4%）。严重不良反应发生在28%的患者中；其中≥2%的包括肺炎（3%）、心肌缺血（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%）为疲劳（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患者中发生的不良反应与接受KEYTRUDA单药治疗的黑色素瘤或NSCLC患者中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研究中，MSI-H或dMMR癌症患者发生的不良反应与接受KEYTRUDA单药治疗的其他实体瘤患者中发生的不良反应相似。

In KEYNOTE-811, fatal adverse reactions occurred in 3 patients who received KEYTRUDA in combination with trastuzumab and CAPOX or FP and included pneumonitis in 2 patients and hepatitis in 1 patient. KEYTRUDA was discontinued due to adverse reactions in 13% of 350 patients with locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma.

在KEYNOTE-811研究中，接受KEYTRUDA联合曲妥珠单抗和CAPOX或FP治疗的患者中有3例发生致命不良反应，其中2例为肺炎，1例为肝炎。在350名局部晚期不可切除或转移性HER2阳性胃癌或胃食管交界处腺癌患者中，有13%因不良反应而停用KEYTRUDA。

Adverse reactions resulting in permanent discontinuation of KEYTRUDA in ≥1% of patients were pneumonitis (2.0%) and pneumonia (1.1%). In the KEYTRUDA arm vs placebo, there was a difference of ≥5% incidence between patients treated with KEYTRUDA vs standard of care for diarrhea (53% vs 47%), rash (35% vs 28%), hypothyroidism (11% vs 5%), and pneumonia (11% vs 5%)..

导致≥1%的患者永久停用KEYTRUDA的不良反应为肺炎（2.0%）和肺部感染（1.1%）。在KEYTRUDA组与安慰剂组中，使用KEYTRUDA治疗的患者与标准治疗相比，发生率差异≥5%的不良反应包括腹泻（53% vs 47%）、皮疹（35% vs 28%）、甲状腺功能减退（11% vs 5%）和肺炎（11% vs 5%）。

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联合化疗的患者中最常见的不良反应（报告率≥20%）包括疲劳/虚弱、恶心、便秘、腹泻、食欲减退、皮疹、呕吐、咳嗽、呼吸困难、发热、脱发、外周神经病变、黏膜炎、口腔炎、头痛、体重减轻、腹痛、关节痛、肌肉痛、失眠、手足红肿综合征、尿路感染和甲状腺功能减退。

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试验中，当KEYTRUDA与含氟嘧啶和铂的化疗联合使用时，在785名患者中有45%发生了严重不良反应。超过2%的患者出现的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%发生了致命的不良反应，其中包括感染（2.3%）和血栓栓塞（1.3%）。由于不良反应，15%的患者永久停用了KEYTRUDA。导致永久停用KEYTRUDA的最常见不良反应（≥1%）为感染（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联合化疗的患者中最常见的不良反应（报告率≥20%）为外周神经病变（47%）、恶心（46%）、疲劳（40%）、腹泻（36%）、呕吐（34%）、食欲减退（29%）、腹痛（26%）、掌跖红斑感觉异常综合征（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试验中，对于不适合手术切除或确定性放化疗的转移性或局部晚期食管或胃食管结合部（肿瘤中心距胃食管结合部1至5厘米）癌患者，当KEYTRUDA与顺铂和氟尿嘧啶一起使用时，在370名患者中有15%因不良反应而停用KEYTRUDA。

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%)..

导致永久停用KEYTRUDA的最常见的不良反应（≥1%）为肺炎（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%）包括恶心（67%）、疲劳（57%）、食欲减退（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单药治疗的食管癌患者发生的不良反应与接受KEYTRUDA单药治疗的黑色素瘤或非小细胞肺癌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研究中，当KEYTRUDA与CRT（顺铂加外照射放疗[EBRT]后接腔内放疗[BT]）联合用于FIGO 2014年分期III-IVA期宫颈癌患者时，在292名患者中，1.4%的患者发生了致死性不良反应，其中包括大肠穿孔、尿脓毒症、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% 的患者发生了严重的不良反应；其中 ≥1% 的包括尿路感染 (2.7%)、尿脓毒症 (1.4%) 和败血症 (1%)。7% 的患者因不良反应停用了 KEYTRUDA。导致永久停药的最常见的不良反应（≥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%)..

对于接受KEYTRUDA联合CRT治疗的患者，最常见的不良反应（≥10%）为恶心（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%）、食欲减退和体重减轻（各17%）、腹痛和发热（各12%）、甲状腺功能亢进、排尿困难、皮疹（各11%）以及盆腔疼痛（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试验中，将KEYTRUDA联合紫杉醇和顺铂或紫杉醇和卡铂，无论是否联合贝伐单抗（n=307），用于治疗持续性、复发性或一线转移性宫颈癌患者，不论肿瘤PD-L1表达状态如何，这些患者此前未接受过化疗，但同时放疗增敏剂使用除外。4.6%的患者发生了致死性不良反应，其中包括3例出血、2例败血症和不明原因导致的死亡，以及各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（伴或不伴贝伐珠单抗）治疗的患者中有50%发生了严重不良反应；其中≥3%的不良反应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%).

因不良反应，15%的患者停止使用KEYTRUDA。导致永久停药的最常见不良反应（≥1%）为结肠炎（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%）为周围神经病变（62%）、脱发（58%）、贫血（55%）、疲劳/乏力（53%）、恶心和中性粒细胞减少（各41%）、腹泻（39%）、高血压和血小板减少（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（24%）、甲状腺功能减退（22%）以及食欲减退（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%)..

对于接受KEYTRUDA联合化疗（伴或不伴贝伐单抗）治疗的患者，最常见的不良反应（≥20%）为周围神经病变（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%），以及皮疹（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研究中，98名既往接受过治疗的复发或转移性宫颈癌患者中有8%因不良反应而停用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%）为疲劳（43%）、肌肉骨骼疼痛（27%）、腹泻（23%）、疼痛和腹痛（各22%）以及食欲减退（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%), pruritus (12%), upper respiratory tract infection (11%), cough (11%), and hypothyroidism (10%)..

在KEYNOTE-394试验中，299名既往接受过治疗的肝细胞癌患者中有13%因不良反应而停用KEYTRUDA。导致永久停用KEYTRUDA的最常见不良反应为腹水（2.3%）。接受KEYTRUDA治疗的患者中最常见的不良反应（≥10%）包括发热（18%）、皮疹（18%）、腹泻（16%）、食欲减退（15%）、瘙痒（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研究中，当KEYTRUDA与吉西他滨和顺铂联合使用时，在529名局部晚期不可切除或转移性胆道癌患者中，15%的患者因不良反应停止使用KEYTRUDA。导致永久停用KEYTRUDA的最常见的不良反应（≥1%）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%)..

导致中断使用KEYTRUDA的不良反应发生在55%的患者中。导致中断KEYTRUDA（≥2%）最常见的不良反应或实验室异常为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研究中，接受KEYTRUDA单药治疗的MCC患者（n=105）发生的不良反应总体上与接受KEYTRUDA治疗的黑色素瘤或NSCLC患者相似。

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试验中，当KEYTRUDA与阿昔替尼联合使用时，在429名患者中有3.3%发生了致死性不良反应。40%的患者发生了严重不良反应，其中最常见的（≥1%）为肝毒性（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%)..

因不良反应导致永久停药的比例为31%；其中仅KEYTRUDA组为13%，仅阿昔替尼组为13%，联合用药组为8%；最常见的不良反应为肝毒性（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%）包括腹泻（56%）、疲劳/乏力（52%）、高血压（48%）、肝毒性（39%）、甲状腺功能减退（35%）、食欲下降（30%）、掌跖红斑感觉异常（28%）、恶心（28%）、口腔炎/黏膜炎（27%）、发声困难（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，20%的接受KEYTRUDA治疗的患者发生了严重不良反应；其中严重不良反应（≥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（各占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%)..

发生了0.2%的致命不良反应，其中包括1例肺炎。在488名患者中，21%因不良反应停用KEYTRUDA；最常见的（≥1%）为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%）包括肌肉骨骼疼痛（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研究中，当KEYTRUDA与化疗（紫杉醇和卡铂）联合用于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%发生了严重不良反应，而接受安慰剂联合化疗的患者中这一比例为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)..

致命的不良反应发生在1.6%接受KEYTRUDA联合化疗的患者中，其中包括COVID-19（0.5%）和心脏骤停（0.3%）。因不良反应而停用KEYTRUDA的患者占14%。接受KEYTRUDA和化疗治疗的患者中出现的不良反应，通常与单独使用KEYTRUDA或单独使用化疗所观察到的相似，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单药治疗的MSI-H或dMMR子宫内膜癌患者发生的不良反应与接受KEYTRUDA单药治疗的黑色素瘤或非小细胞肺癌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.

在TMB-H癌症患者中发生的不良反应与接受KEYTRUDA单药治疗的其他实体瘤患者中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.

在复发性或转移性 cSCC 或局部晚期 cSCC 患者中发生的不良反应与接受 KEYTRUDA 单药治疗的黑色素瘤或 NSCLC 患者中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试验中，对于新诊断、既往未接受过治疗的高风险早期三阴性乳腺癌（TNBC）患者，将KEYTRUDA与新辅助化疗（卡铂和紫杉醇，随后使用多柔比星或表柔比星和环磷酰胺）联用，接着进行手术，并继续使用KEYTRUDA单药进行辅助治疗（n=778），0.9%的患者发生了致命的不良反应，其中包括各1例肾上腺危象、自身免疫性脑炎、肝炎、肺炎、肺炎、肺栓塞、败血症（伴有多器官功能障碍综合征）以及心肌梗死。

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；其中≥2%的不良反应为发热性中性粒细胞减少（15%）、发热（3.7%）、贫血（2.6%）和中性粒细胞减少（2.2%）。因不良反应，20%的患者停用了KEYTRUDA。导致永久停药的最常见不良反应（≥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治疗的患者中最常见的不良反应（≥20%）包括疲劳（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%）、食欲减退（23%）、失眠（21%）以及肌肉疼痛（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研究中，当KEYTRUDA与化疗（紫杉醇、白蛋白结合型紫杉醇或吉西他滨和卡铂）联合用于既往未接受过转移性治疗的局部复发不可切除或转移性三阴性乳腺癌（TNBC）患者（n=596）时，2.5%的患者发生了致死性不良反应，其中包括心肺骤停（0.7%）和脓毒性休克（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；其中≥2%的严重不良反应为肺炎（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。导致永久停药的最常见反应（≥1%）为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联合化疗的患者中最常见的不良反应（≥20%）为疲劳（48%）、恶心（44%）、脱发（34%）、腹泻和便秘（各28%）、呕吐和皮疹（各26%）、咳嗽（23%）、食欲减退（21%）以及头痛（20%）。

Lactation

泌乳

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出现严重的不良反应，建议女性在治疗期间和最后一剂后的4个月内不要进行母乳喂养。

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 研究中，173 名儿科患者（65 名年龄为 6 个月至未满 12 岁的儿科患者和 108 名年龄为 12 岁至 17 岁的儿科患者）每 3 周接受一次 2 mg/kg 的 KEYTRUDA 治疗。暴露的中位持续时间为 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 (30%), 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，儿科患者中发生率高出≥10%的不良反应包括发热（33%）、白细胞减少（30%）、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%）以及白细胞计数减少（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564名接受KEYTRUDA联合enfortumab vedotin治疗的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岁及以上患者和较年轻患者之间，未观察到安全性和有效性方面的总体差异。

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..

接受KEYTRUDA联合enfortumab vedotin治疗的75岁及以上患者，其致命不良反应的发生率高于较年轻的患者。在75岁以下的患者中，致命不良反应的发生率为4%，而在75岁及以上的患者中，这一比例为7%。

Additional Selected KEYTRUDA Indications in the U.S.

美国KEYTRUDA的其他选定适应症

Melanoma

黑色素瘤

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

KEYTRUDA 适用于治疗无法切除或转移性黑色素瘤的患者。

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 适用于成人和 12 岁及以上儿童的 IIB、IIC 或 III 期黑色素瘤患者在完全切除后的辅助治疗。

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，适用于一线治疗无EGFR或ALK基因组肿瘤畸变的转移性非鳞状非小细胞肺癌（NSCLC）患者。

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型，适用于转移性鳞状非小细胞肺癌患者的一线治疗。

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单药适用于表达PD-L1（肿瘤比例评分（TPS）≥1%）且经FDA批准的检测方法确定无EGFR或ALK基因组肿瘤异常的非小细胞肺癌（NSCLC）患者的一线治疗，且：

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的放化疗，或者

metastatic.

转移性的。

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单药适用于治疗肿瘤表达PD-L1（TPS≥1%）的转移性非小细胞肺癌患者，需经FDA批准的检测方法确定，并且在含铂化疗期间或之后疾病进展。携带EGFR或ALK基因组肿瘤异常的患者在接受KEYTRUDA之前，应在接受针对这些异常的FDA批准的治疗后出现疾病进展。

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厘米或淋巴结阳性）的非小细胞肺癌患者，与含铂化疗联合使用作为新辅助治疗，然后在手术后继续作为单一药物进行辅助治疗。

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单药适用于成人IB期（T2a ≥4 cm）、II期或IIIA期非小细胞肺癌患者在手术切除及铂类化疗后的辅助治疗。

Malignant Pleural Mesothelioma

恶性胸膜间皮瘤

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic malignant pleural mesothelioma (MPM).

KEYTRUDA联合培美曲塞和铂类化疗，适用于成人不可切除的晚期或转移性恶性胸膜间皮瘤（MPM）的一线治疗。

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联合铂类和氟尿嘧啶（FU），适用于转移性或不可切除、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单药适用于一线治疗肿瘤表达PD-L1（综合阳性评分[CPS]≥1）的转移性或不可切除、复发性头颈部鳞状细胞癌（HNSCC）患者，需由FDA批准的检测方法确定。

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单药适用于治疗在含铂化疗期间或之后疾病进展的复发性或转移性HNSCC患者。

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 适用于治疗患有难治性 cHL，或在接受两种或更多种疗法后复发的 cHL 的儿科患者。

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 适用于治疗患有难治性原发性纵隔大B细胞淋巴瘤（PMBCL）的成人和儿童患者，或已在接受2种或更多先前治疗方案后复发的患者。对于需要紧急细胞减灭治疗的PMBCL患者，不推荐使用 KEYTRUDA。

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联合enfortumab vedotin适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单药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

谁不符合任何含铂化疗的条件，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，或在含铂化疗的新辅助治疗或辅助治疗后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单药适用于治疗卡介苗（BCG）无反应、高风险、非肌层浸润性膀胱癌（NMIBC）伴原位癌（CIS）的患者，无论是否伴有乳头状肿瘤，且这些患者不适合或选择不进行膀胱切除术。

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 适用于治疗经 FDA 批准的检测方法确定的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) 实体瘤的成人和儿童患者，这些患者在先前治疗后病情进展且没有满意的替代治疗方案。

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

微卫星不稳定性高或错配修复缺陷结直肠癌

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.

KEYTRUDA 适用于治疗由 FDA 批准的检测方法确定的不可切除或转移性 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，适用于一线治疗局部晚期不可切除或转移性HER2阳性胃或胃食管交界处（GEJ）腺癌成人患者，其肿瘤表达PD-L1（CPS≥1），需通过FDA批准的检测方法确定。

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 whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test..

KEYTRUDA联合含氟嘧啶和铂的化疗，适用于一线治疗局部晚期不可切除或转移性HER2阴性的胃或胃食管交界处（GEJ）腺癌成人患者，其肿瘤表达PD-L1（CPS≥1），需通过FDA批准的检测方法确定。

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) 癌症（肿瘤中心位于 GEJ 以上 1 至 5 厘米处），且无法通过手术切除或确定性放化疗治疗的患者：

in combination with platinum- and fluoropyrimidine-based chemotherapy for patients with tumors that express PD-L1 (CPS ≥ 1), or

与基于铂和氟嘧啶的化疗联合使用，适用于表达PD-L1（CPS ≥ 1）的肿瘤患者，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.

作为单一药物用于治疗经一种或多种先前系统治疗后，由FDA批准的检测方法确定为PD-L1（CPS≥10）表达的鳞状细胞组织学肿瘤患者。

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）适用于治疗FIGO 2014分期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，无论是否使用贝伐单抗，适用于治疗肿瘤表达PD-L1（CPS≥1）的持续性、复发性或转移性宫颈癌患者，PD-L1表达情况需由FDA批准的检测方法确定。

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单药适用于治疗化疗期间或之后疾病进展的复发性或转移性宫颈癌患者，其肿瘤表达PD-L1（CPS≥1），需通过FDA批准的检测方法确定。

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 适用于治疗先前接受过除 PD-1/PD-L1 方案以外的其他系统治疗的乙型肝炎继发肝细胞癌 (HCC) 患者。

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联合吉西他滨和顺铂，适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默克尔细胞癌 (MCC) 的成人和儿童患者。

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联合阿昔替尼适用于晚期肾细胞癌（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 适用于在肾切除术后或肾切除术及转移病灶切除术后，对复发风险为中高危或高危的肾细胞癌 (RCC) 患者进行辅助治疗。

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，随后KEYTRUDA单药治疗，适用于治疗原发性晚期或复发性子宫内膜癌的成年患者。

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单药适用于治疗经FDA批准的检测方法确定为MSI-H或dMMR的晚期子宫内膜癌成人患者，这些患者在任何治疗环境下接受先前系统治疗后疾病进展，并且不适合进行根治性手术或放疗。

Tumor Mutational Burden-High Cancer

高肿瘤突变负荷癌症

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 适用于治疗不可切除或转移性肿瘤突变负荷高（TMB-H）[≥10 个突变/兆碱基（mut/Mb）]的成人和儿童实体瘤患者，这些患者经 FDA 批准的检测方法确定，在先前治疗后疾病进展，并且没有满意的替代治疗方案。

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..

该适应症是基于肿瘤反应率和反应持久性获得加速批准的。此适应症的持续批准可能取决于在确证性试验中对临床益处的验证和描述。KEYTRUDA 在 TMB-H 中枢神经系统癌症的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 适用于治疗复发性或转移性皮肤鳞状细胞癌 (cSCC) 或无法通过手术或放疗治愈的局部晚期 cSCC 患者。

Please see Prescribing Information for KEYTRUDA (pembrolizumab) at

有关KEYTRUDA（pembrolizumab）的处方信息，请参见

http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf

http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf

and Medication Guide for KEYTRUDA at

和KEYTRUDA的药物指南 tại

http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf

http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf

.

。

Merck’s focus on cancer

默克公司对癌症的关注

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.

每一天，我们都遵循科学规律，努力发现能够帮助患者的创新方法，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，我们正在追求科学机遇与医疗需求交汇点上的研究，这得益于我们多样化的、包含25种以上新型机制的研发管线。

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.

通过在超过30种肿瘤类型中开展规模最大的临床开发项目之一，我们致力于推动突破性科学发展，以塑造肿瘤学的未来。通过解决参与临床试验、筛查和治疗的障碍，我们紧急行动以减少差异，确保患者能够获得高质量的癌症治疗。

Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer. For more information, visit .

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。欲了解更多信息，请访问。

www.merck.com/research/oncology

www.merck.com/research/oncology

.

。

About Merck

关于默克公司

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.

在默克（在美国和加拿大以外地区称为MSD），我们围绕一个使命团结一致：我们利用前沿科学的力量来拯救生命并改善世界各地人们的生活。一个多世纪以来，我们通过开发重要的药物和疫苗，为人类带来了希望。

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.

我们立志成为全球首屈一指的研究密集型生物制药公司——如今，我们站在研究的最前沿，致力于提供创新的健康解决方案，推动人类和动物疾病预防与治疗的进步。我们培养多元化和包容性的全球员工队伍，并每天以负责任的方式运营，以确保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 .

欲了解更多信息，请访问。

www.merck.com

www.merck.com

and connect with us on

并关注我们

X (formerly Twitter)

X（前称Twitter）

,

，

Facebook

Facebook

,

，

Instagram

图享

,

，

YouTube

YouTube

and

和

LinkedIn

领英

.

。

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

美国新泽西州拉威市默克公司前瞻性声明

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.

本新闻稿由美国新泽西州拉威市的默克公司（Merck & Co., Inc.，以下简称“公司”）发布，包含根据1995年《美国私人证券诉讼改革法案》安全港条款定义的“前瞻性声明”。这些声明基于公司管理层当前的信念和期望，但受重大风险和不确定性的影响。

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，无法保证这些候选人将获得必要的监管批准，或证明其具有商业上的成功。如果基本假设被证明不准确或风险或不确定性成为现实，实际结果可能与前瞻性陈述中所述的结果有重大差异。

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 innovative 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：行业总体状况和竞争；经济总体因素，包括利率和汇率波动；美国及国际制药行业监管和医疗保健立法的影响；全球医疗成本控制趋势；技术进步以及竞争对手获得的新产品和专利；新产品开发的固有挑战，包括获得监管批准；公司准确预测未来市场状况的能力；生产困难或延误；国际经济的财务不稳定性和主权风险；对创新产品依赖于公司专利及其他保护措施的有效性；以及面临诉讼（包括专利诉讼）和/或监管行动的风险。

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, 2024 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (.

公司不承担公开更新任何前瞻性声明的义务，无论这是由于新信息、未来事件或其他原因。可能导致结果与前瞻性声明中描述的情况有重大差异的其他因素，可以在公司截至 2024 年 12 月 31 日的年度报告（Form 10-K）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 的官方网站上查阅。

www.sec.gov

www.sec.gov

).

）。

Media Contacts:

媒体联系人：

Julie Cunningham

朱莉·坎宁安

(617) 519-6264

(617) 519-6264

Marian Cutler

玛丽安·卡特勒

(973) 517-0519

(973) 517-0519

Investor Contacts:

投资者联系人：

Peter Dannenbaum

彼得·丹嫩鲍姆

(732) 594-1579

(732) 594-1579

Steven Graziano

史蒂文·格拉齐亚诺

(732) 594-1583

(732) 594-1583

Source: Merck & Co., Inc.

来源：默克公司