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RAHWAY, N.J. & FOSTER CITY, Calif.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside of the United States and Canada, and Gilead Sciences, Inc. (Nasdaq: GILD) today announced the discontinuation of the Phase 3 KEYNOTE-D46/EVOKE-03 study investigating Gilead’s Trodelvy® (sacituzumab govitecan-hziy) in combination with KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, compared to KEYTRUDA monotherapy in certain patients with previously untreated metastatic non-small cell lung cancer, whose tumors expressed PD-L1 (tumor proportion score [TPS] ≥50%). The decision is based on the recommendation from the external Data Monitoring Committee (eDMC) following their review of the data from the pre-specified final analysis of progression-free survival (PFS) and interim analysis of overall survival (OS).

新泽西州拉瓦伊 & 加州福斯特城 --（商业资讯）-- 默克（NYSE: MRK），在美国和加拿大以外称为 MSD，和吉利德科学公司（Nasdaq: GILD）今天宣布停止进行第 3 期 KEYNOTE-D46/EVOKE-03 研究，该研究调查吉利德的 Trodelvy®（sacituzumab govitecan-hziy）与默克的抗 PD-1 疗法 KEYTRUDA®（pembrolizumab）联合使用，与 KEYTRUDA 单药治疗相比，在某些之前未接受治疗的转移性非小细胞肺癌患者中进行，该患者的肿瘤表达 PD-L1（肿瘤比例评分 [TPS] ≥50%）。这一决定是基于外部数据监测委员会（eDMC）在审查了无进展生存期（PFS）预设最终分析和总体生存期（OS）中期分析的数据后提出的建议。

A numerical improvement in PFS was observed, but did not reach statistical significance. The probability of achieving statistically significant OS is unlikely at the planned final analysis. The safety profile of Trodelvy in combination with KEYTRUDA was consistent with the known safety of each agent. No new safety signals were identified with the combination. These data will be presented at a future medical meeting.

观察到 PFS 有数值改善，但未达到统计学显著性。在计划的最终分析中，达到统计学显著的 OS 的可能性不大。Trodelvy 与 KEYTRUDA 联合使用的安全性特征与已知的每种药物的安全性一致。未发现新的安全信号。这些数据将在未来的医学会议上进行展示。

Regulatory authorities have been informed. Merck will inform study investigators of the recommendation from the DMC and advise patients in the study to speak to their physician regarding treatment. There are no changes to ongoing Trodelvy or Merck studies.

监管机构已被告知。默克将通知研究调查员 DMC 的建议，并建议研究中的患者与其医生讨论治疗方案。正在进行的 Trodelvy 或默克研究没有变化。

The companies are grateful to the patients, families, and healthcare professionals who participated in the KEYNOTE-D46/EVOKE-03 study and contributed to this important work.

公司对参与 KEYNOTE-D46/EVOKE-03 研究并为这项重要工作做出贡献的患者、家庭和医疗专业人员表示感谢。

Trodelvy is a registered trademark of Gilead Sciences, Inc., or its related companies.

Trodelvy 是吉利德科学公司或其相关公司的注册商标。

KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

KEYTRUDA®是默克 Sharp & Dohme LLC 的注册商标，该公司是默克公司（Merck & Co., Inc.）的子公司，位于美国新泽西州拉瓦伊。

About Metastatic Non-Small Cell Lung Cancer

关于转移性非小细胞肺癌

Lung cancer is one of the most common cancers worldwide, with an estimated 2.5 million new cases reported globally in 2022. Non-small cell lung cancer (NSCLC) accounts for approximately 80% to 85% of lung cancers, and nearly half of these NSCLC patients are diagnosed only after the disease has spread, when treatment options are more limited and long-term survival remains low. Despite treatment advances, the 5-year survival rate for metastatic NSCLC is less than 10%. While immunotherapy, with or without chemotherapy, is a standard first treatment option, it does not work for everyone, and new treatment options are needed.

肺癌是全球最常见的癌症之一，2022 年全球报告的新病例估计为 250 万例。非小细胞肺癌（NSCLC）约占肺癌的 80% 至 85%，而这些 NSCLC 患者中近一半是在疾病扩散后才被诊断，此时治疗选择更为有限，长期生存率仍然较低。尽管治疗有所进展，转移性 NSCLC 的 5 年生存率仍低于 10%。虽然免疫疗法（无论是否联合化疗）是标准的首选治疗方案，但并非对所有人有效，因此需要新的治疗选择。

About KEYNOTE-D46/EVOKE-03

关于 KEYNOTE-D46/EVOKE-03

The KEYNOTE-D46/EVOKE-03 study is a global, open-label, randomized Phase 3 trial, sponsored by Merck, evaluating the efficacy and safety of Trodelvy (sacituzumab govitecan-hziy) in combination with KEYTRUDA (pembrolizumab) compared with KEYTRUDA monotherapy in patients with previously untreated metastatic non-small cell lung cancer (mNSCLC) whose tumors express PD-L1 with a tumor proportion score (TPS) ≥50% and do not have sensitizing EGFR, ALK or ROS1 genomic alterations. Approximately 620 patients were enrolled across study sites worldwide.

KEYNOTE-D46/EVOKE-03 研究是一项全球开放标签随机第 3 期试验，由默克赞助，评估 Trodelvy（sacituzumab govitecan-hziy）与 KEYTRUDA（pembrolizumab）联合使用与 KEYTRUDA 单药治疗在之前未接受治疗的转移性非小细胞肺癌（mNSCLC）患者中的疗效和安全性，这些患者的肿瘤表达 PD-L1，肿瘤比例评分（TPS）≥50%，且没有敏感的 EGFR、ALK 或 ROS1 基因改变。大约 620 名患者在全球研究地点入组。

Patients were randomized 1:1 to receive either Trodelvy (10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle) plus KEYTRUDA (200 mg intravenously on Day 1 of a 21-day cycle), or KEYTRUDA monotherapy (200 mg intravenously on Day 1 of a 21-day cycle). KEYTRUDA was administered for up to 35 cycles, and Trodelvy was continued until disease progression, death, unacceptable toxicity or another treatment discontinuation criterion was met.

患者按 1:1 随机分配，接受 Trodelvy（在 21 天周期的第 1 天和第 8 天静脉注射 10 mg/kg）加 KEYTRUDA（在 21 天周期的第 1 天静脉注射 200 mg），或 KEYTRUDA 单药治疗（在 21 天周期的第 1 天静脉注射 200 mg）。KEYTRUDA 的给药持续最多 35 个周期，Trodelvy 则持续至疾病进展、死亡、不可接受的毒性或满足其他治疗中断标准。

The dual primary endpoints of the study are progression-free survival (PFS) as assessed by blinded independent central review (BICR) according to RECIST v1.1, and overall survival (OS). Secondary endpoints include objective response rate (ORR), duration of response (DOR), patient-reported outcomes (PROs) and safety. More information about the study is available at ClinicalTrials.gov: NCT05609968.

该研究的两个主要终点是通过盲法独立中央审查（BICR）根据 RECIST v1.1 评估的无进展生存期（PFS）和总体生存期（OS）。次要终点包括客观缓解率（ORR）、缓解持续时间（DOR）、患者报告结果（PROs）和安全性。有关该研究的更多信息，请访问 ClinicalTrials.gov：NCT05609968。

About Trodelvy

关于 Trodelvy

Trodelvy (sacituzumab govitecan-hziy) is a first-in-class Trop-2-directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast and lung cancers. Trodelvy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the tumor microenvironment through a bystander effect.

Trodelvy（sacituzumab govitecan-hziy）是一种首创的针对 Trop-2 的抗体药物偶联物。Trop-2 是一种在多种肿瘤类型中高度表达的细胞表面抗原，包括超过 90% 的乳腺癌和肺癌。Trodelvy 的设计采用了一种专有的可水解连接子，连接到 SN-38，这是一种拓扑异构酶 I 抑制剂。这种独特的组合通过旁观者效应向 Trop-2 表达细胞和肿瘤微环境提供强效活性。

Trodelvy is currently approved in more than 60 countries for second-line or later metastatic triple-negative breast cancer (TNBC) and in more than 50 countries for certain patients with pre-treated HR+/HER2- metastatic breast cancer (mBC). Healthcare professionals have well-established experience with Trodelvy, which has shown generally consistent outcomes across both clinical trials and real-world use in more than 75,000 breast cancer patients across 60+ countries.

Trodelvy 目前在 60 多个国家获得批准，用于二线或后续治疗的转移性三阴性乳腺癌（TNBC），并在 50 多个国家用于某些接受过治疗的 HR+/HER2-转移性乳腺癌（mBC）患者。医疗专业人员对 Trodelvy 有良好的经验，该药在 60 多个国家的 75,000 多名乳腺癌患者的临床试验和真实世界使用中显示出普遍一致的结果。

Trodelvy is currently being evaluated in multiple ongoing Phase 3 trials across a range of tumor types with high Trop-2 expression. These studies with Trodelvy, both in monotherapy and in combination with pembrolizumab, involve earlier lines of treatment for TNBC and HR+/HER2- breast cancer—including in curative settings—as well as in small cell lung and gynecologic cancers, where previous proof-of-concept studies have demonstrated clinical activity.

Trodelvy 目前正在多个正在进行的第 3 期试验中评估，涉及高 Trop-2 表达的多种肿瘤类型。这些与 Trodelvy 相关的研究，包括单药治疗和与 pembrolizumab 联合使用，涉及 TNBC 和 HR+/HER2-乳腺癌的早期治疗方案——包括在治愈性设置中——以及小细胞肺癌和妇科癌症，其中之前的概念验证研究已证明了临床活性。

Indications for Trodelvy

Trodelvy 的适应症

TRODELVY® (sacituzumab govitecan-hziy) is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:

TRODELVY®（sacituzumab govitecan-hziy）是一种针对 Trop-2 的抗体和拓扑异构酶抑制剂偶联物，适用于治疗成年患者：

Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease.

不可切除的局部晚期或转移性三阴性乳腺癌（mTNBC），已接受两种或更多先前的系统治疗，其中至少一种用于转移性疾病。

Unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.

不可切除的局部晚期或转移性激素受体（HR）阳性、人体表皮生长因子受体 2（HER2）阴性（IHC 0、IHC 1+ 或 IHC 2+/ISH–）乳腺癌患者，已接受基于内分泌的治疗和至少两种额外的系统治疗。

U.S. Important safety information FOR TRODELVY

美国 TRODELVY 重要安全信息

BOXED WARNING: NEUTROPENIA AND DIARRHEA

警示框：中性粒细胞减少症和腹泻

TRODELVY can cause severe, life-threatening, or fatal neutropenia. Withhold TRODELVY for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment. Primary prophylaxis with G-CSF is recommended for all patients at increased risk of febrile neutropenia. Initiate anti-infective treatment in patients with febrile neutropenia without delay.

TRODELVY 可能导致严重、危及生命或致命的中性粒细胞减少症。对于绝对中性粒细胞计数低于 1500/mm3 或中性粒细胞减少性发热的患者，应暂停使用 TRODELVY。在治疗期间定期监测血细胞计数。建议对所有有发热性中性粒细胞减少症风险的患者进行 G-CSF 的初级预防。对发热性中性粒细胞减少症患者应及时启动抗感染治疗。

TRODELVY can cause severe diarrhea. Monitor patients with diarrhea and give fluid and electrolytes as needed. At the onset of diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide. If severe diarrhea occurs, withhold TRODELVY until resolved to ≤ Grade 1 and reduce subsequent doses.

TRODELVY 可能导致严重腹泻。监测腹泻患者，并根据需要补充液体和电解质。腹泻发生时，评估感染原因，如果结果为阴性，及时启动洛哌丁胺。如果发生严重腹泻，应暂停使用 TRODELVY，直到恢复至 ≤ 1 级，并减少后续剂量。

CONTRAINDICATIONS

禁忌症

Severe hypersensitivity reaction to TRODELVY.

对 TRODELVY 的严重过敏反应。

WARNINGS AND PRECAUTIONS

警告和注意事项

Neutropenia: Severe, life-threatening, or fatal neutropenia can occur as early as the first cycle of treatment and may require dose modification. Neutropenia occurred in 64% of patients treated with TRODELVY. Grade 3-4 neutropenia occurred in 49% of patients. Febrile neutropenia occurred in 6%. Neutropenic colitis occurred in 1.4%. Primary prophylaxis with G-CSF is recommended starting in the first cycle of treatment in all patients at increased risk of febrile neutropenia, including older patients, patients with previous neutropenia, poor performance status, organ dysfunction, or multiple comorbidities. Monitor absolute neutrophil count (ANC) during treatment. Withhold TRODELVY for ANC below 1500/mm3 on Day 1 of any cycle or below 1000/mm3 on Day 8 of any cycle. Withhold TRODELVY for neutropenic fever. Treat neutropenia with G-CSF and administer prophylaxis in subsequent cycles as clinically indicated or indicated in Table 2 of USPI.

中性粒细胞减少症： 严重、危及生命或致命的中性粒细胞减少症可能在治疗的第一个周期就发生，并可能需要调整剂量。接受 TRODELVY 治疗的患者中有 64% 发生了中性粒细胞减少症。3-4 级中性粒细胞减少症发生在 49% 的患者中。发热性中性粒细胞减少症发生在 6% 的患者中。中性粒细胞减少性结肠炎发生在 1.4% 的患者中。建议在所有有发热性中性粒细胞减少症风险的患者中，从治疗的第一个周期开始使用 G-CSF 进行初级预防，包括老年患者、既往有中性粒细胞减少症的患者、表现状态差、器官功能障碍或多种合并症的患者。在治疗期间监测绝对中性粒细胞计数（ANC）。在任何周期的第 1 天 ANC 低于 1500/mm3 或在任何周期的第 8 天低于 1000/mm3 时应暂停使用 TRODELVY。对于中性粒细胞减少性发热应暂停使用 TRODELVY。用 G-CSF 治疗中性粒细胞减少症，并在后续周期中根据临床需要或根据 USPI 表 2 的指示进行预防。

Diarrhea: Diarrhea occurred in 64% of all patients treated with TRODELVY. Grade 3-4 diarrhea occurred in 11% of patients. One patient had intestinal perforation following diarrhea. Diarrhea that led to dehydration and subsequent acute kidney injury occurred in 0.7% of all patients. Withhold TRODELVY for Grade 3-4 diarrhea and resume when resolved to ≤ Grade 1. At onset, evaluate for infectious causes and if negative, promptly initiate loperamide, 4 mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may also be employed as clinically indicated. Patients who exhibit an excessive cholinergic response to treatment can receive appropriate premedication (e.g., atropine) for subsequent treatments.

腹泻： 所有接受 TRODELVY 治疗的患者中有 64% 发生了腹泻。3-4 级腹泻发生在 11% 的患者中。有一名患者在腹泻后发生肠穿孔。导致脱水和随后的急性肾损伤的腹泻发生在所有患者中的 0.7%。对于 3-4 级腹泻应暂停使用 TRODELVY，并在恢复至 ≤ 1 级时重新开始。发生时，评估感染原因，如果结果为阴性，及时启动洛哌丁胺，初始剂量为 4 毫克，随后每次腹泻 2 毫克，最大每日剂量为 16 毫克。腹泻缓解后 12 小时停止使用洛哌丁胺。根据临床需要，还可以采取其他支持措施（例如，液体和电解质替代）。对治疗表现出过度胆碱能反应的患者可以在后续治疗中给予适当的预药（例如，阿托品）。

Hypersensitivity and Infusion-Related Reactions: TRODELVY can cause serious hypersensitivity reactions including life-threatening anaphylactic reactions. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions. Hypersensitivity reactions within 24 hours of dosing occurred in 35% of patients. Grade 3-4 hypersensitivity occurred in 2% of patients. The incidence of hypersensitivity reactions leading to permanent discontinuation of TRODELVY was 0.2%. The incidence of anaphylactic reactions was 0.2%. Pre-infusion medication is recommended. Have medications and emergency equipment to treat such reactions available for immediate use. Observe patients closely for hypersensitivity and infusion-related reactions during each infusion and for at least 30 minutes after completion of each infusion. Permanently discontinue TRODELVY for Grade 4 infusion-related reactions.

过敏反应和输注相关反应： TRODELVY 可能导致严重的过敏反应，包括危及生命的过敏性反应。严重的体征和症状包括心脏骤停、低血压、喘息、血管神经性水肿、肿胀、肺炎和皮肤反应。给药后 24 小时内发生的过敏反应在 35% 的患者中出现。3-4 级过敏反应发生在 2% 的患者中。导致永久停用 TRODELVY 的过敏反应发生率为 0.2%。过敏性反应的发生率为 0.2%。建议进行预输注用药。应准备好药物和急救设备以便立即处理此类反应。在每次输注期间及输注完成后至少 30 分钟内密切观察患者是否出现过敏和输注相关反应。对于 4 级输注相关反应应永久停用 TRODELVY。

Nausea and Vomiting: TRODELVY is emetogenic and can cause severe nausea and vomiting. Nausea occurred in 64% of all patients treated with TRODELVY and Grade 3-4 nausea occurred in 3% of these patients. Vomiting occurred in 35% of patients and Grade 3-4 vomiting occurred in 2% of these patients. Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV). Withhold TRODELVY doses for Grade 3 nausea or Grade 3-4 vomiting and resume with additional supportive measures when resolved to Grade ≤ 1 . Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting.

恶心和呕吐： TRODELVY 具有致吐性，可能导致严重的恶心和呕吐。所有接受 TRODELVY 治疗的患者中有 64% 发生了恶心，3-4 级恶心发生在 3% 的患者中。35% 的患者发生了呕吐，3-4 级呕吐发生在 2% 的患者中。建议使用两种或三种药物组合（例如，地塞米松与 5-HT3 受体拮抗剂或 NK1 受体拮抗剂以及其他药物）进行化疗引起的恶心和呕吐（CINV）的预防。对于 3 级恶心或 3-4 级呕吐应暂停使用 TRODELVY，并在恢复至 ≤ 1 级时与额外的支持措施一起恢复。根据临床需要，还可以使用其他止吐药和其他支持措施。所有患者应获得带有明确说明的带回家药物，以预防和治疗恶心和呕吐。

Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity: Patients homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia and may be at increased risk for other adverse reactions with TRODELVY. The incidence of Grade 3-4 neutropenia was 58% in patients homozygous for the UGT1A1*28, 49% in patients heterozygous for the UGT1A1*28 allele, and 43% in patients homozygous for the wild-type allele. The incidence of Grade 3-4 anemia was 21% in patients homozygous for the UGT1A1*28 allele, 10% in patients heterozygous for the UGT1A1*28 allele, and 9% in patients homozygous for the wild-type allele. Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue TRODELVY based on clinical assessment of the onset, duration and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate reduced UGT1A1 function.

UGT1A1 活性降低患者的不良反应风险增加： 同型合子携带尿苷二磷酸 - 葡萄糖醛酸转移酶 1A1（UGT1A1）*28 等位基因的患者中性粒细胞减少症、发热性中性粒细胞减少症和贫血的风险增加，并可能面临其他不良反应的风险。UGT1A1*28 同型合子的 3-4 级中性粒细胞减少症发生率为 58%，UGT1A1*28 杂合子的发生率为 49%，野生型等位基因同型合子的发生率为 43%。UGT1A1*28 同型合子的 3-4 级贫血发生率为 21%，UGT1A1*28 杂合子的发生率为 10%，野生型等位基因同型合子的发生率为 9%。密切监测已知 UGT1A1 活性降低的患者的不良反应。根据临床评估观察到的不良反应的发生、持续时间和严重程度，决定是否暂停或永久停用 TRODELVY，特别是在出现急性早发或异常严重的不良反应时，这可能表明 UGT1A1 功能降低。

Embryo-Fetal Toxicity: Based on its mechanism of action, TRODELVY can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. TRODELVY contains a genotoxic component, SN-38, and targets rapidly dividing cells. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TRODELVY and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TRODELVY and for 3 months after the last dose.

胚胎 - 胎儿毒性： 根据其作用机制，TRODELVY 在孕妇中使用时可能导致致畸和/或胚胎 - 胎儿致死。TRODELVY 含有基因毒性成分 SN-38，并针对快速分裂的细胞。建议孕妇和具有生育潜力的女性注意对胎儿的潜在风险。在使用 TRODELVY 治疗期间及最后一次给药后 6 个月内，建议具有生育潜力的女性使用有效的避孕措施。建议与具有生育潜力的女性伴侣的男性患者在使用 TRODELVY 治疗期间及最后一次给药后 3 个月内使用有效的避孕措施。

ADVERSE REACTIONS

不良反应

In the pooled safety population, the most common (≥ 25%) adverse reactions including laboratory abnormalities were decreased leukocyte count (84%), decreased neutrophil count (75%), decreased hemoglobin (69%), diarrhea (64%), nausea (64%), decreased lymphocyte count (63%), fatigue (51%), alopecia (45%), constipation (37%), increased glucose (37%), decreased albumin (35%), vomiting (35%), decreased appetite (30%), decreased creatinine clearance (28%), increased alkaline phosphatase (28%), decreased magnesium (27%), decreased potassium (26%), and decreased sodium (26%).

在汇总的安全人群中，最常见（≥ 25%）的不良反应包括实验室异常，白细胞计数减少（84%），中性粒细胞计数减少（75%），血红蛋白减少（69%），腹泻（64%），恶心（64%），淋巴细胞计数减少（63%），疲劳（51%），脱发（45%），便秘（37%），血糖升高（37%），白蛋白减少（35%），呕吐（35%），食欲减退（30%），肌酐清除率减少（28%），碱性磷酸酶升高（28%），镁减少（27%），钾减少（26%），和钠减少（26%）。

In the ASCENT study (locally advanced or metastatic triple-negative breast cancer), the most common adverse reactions (incidence ≥25%) were fatigue, diarrhea, nausea, alopecia, constipation, vomiting, abdominal pain, and decreased appetite. The most frequent serious adverse reactions (SAR) (>1%) were neutropenia (7%), diarrhea (4%), and pneumonia (3%). SAR were reported in 27% of patients, and 5% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the ASCENT study were reduced neutrophils, leukocytes, and lymphocytes.

在 ASCENT 研究（局部晚期或转移性三阴性乳腺癌）中，最常见的不良反应（发生率 ≥25%）为疲劳、腹泻、恶心、脱发、便秘、呕吐、腹痛和食欲减退。最常见的严重不良反应（SAR）（>1%）为中性粒细胞减少（7%）、腹泻（4%）和肺炎（3%）。27% 的患者报告了 SAR，5% 的患者因不良反应中止治疗。ASCENT 研究中最常见的 3-4 级实验室异常（发生率 ≥25%）为中性粒细胞、白细胞和淋巴细胞减少。

In the TROPiCS-02 study (locally advanced or metastatic HR-positive, HER2-negative breast cancer), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, nausea, alopecia, and constipation. The most frequent serious adverse reactions (SAR) (>1%) were diarrhea (5%), febrile neutropenia (4%), neutropenia (3%), abdominal pain, colitis, neutropenic colitis, pneumonia, and vomiting (each 2%). SAR were reported in 28% of patients, and 6% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPiCS-02 study were reduced neutrophils and leukocytes.

在 TROPiCS-02 研究（局部晚期或转移性 HR 阳性、HER2 阴性乳腺癌）中，最常见的不良反应（发生率 ≥25%）为腹泻、疲劳、恶心、脱发和便秘。最常见的严重不良反应（SAR）（>1%）为腹泻（5%）、发热性中性粒细胞减少（4%）、中性粒细胞减少（3%）、腹痛、结肠炎、中性粒细胞减少性结肠炎、肺炎和呕吐（各 2%）。28% 的患者报告了 SAR，6% 的患者因不良反应中止治疗。TROPiCS-02 研究中最常见的 3-4 级实验室异常（发生率 ≥25%）为中性粒细胞和白细胞减少。

DRUG INTERACTIONS

药物相互作用

UGT1A1 Inhibitors: Concomitant administration of TRODELVY with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38. Avoid administering UGT1A1 inhibitors with TRODELVY.

UGT1A1 抑制剂： 与 UGT1A1 抑制剂同时使用 TRODELVY 可能会增加不良反应的发生率，因为可能会增加 SN-38 的全身暴露。避免与 TRODELVY 同时使用 UGT1A1 抑制剂。

UGT1A1 Inducers: Exposure to SN-38 may be reduced in patients concomitantly receiving UGT1A1 enzyme inducers. Avoid administering UGT1A1 inducers with TRODELVY.

UGT1A1 诱导剂： 同时接受 UGT1A1 酶诱导剂的患者可能会减少对 SN-38 的暴露。避免与 TRODELVY 同时使用 UGT1A1 诱导剂。

Please see full Prescribing Information , including BOXED WARNING.

请参阅完整的 处方信息 ，包括警示说明。

About KEYTRUDA® (pembrolizumab) injection for intravenous use, 100 mg

关于 KEYTRUDA®（帕博利珠单抗）静脉注射，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，通过增强身体免疫系统检测和对抗肿瘤细胞的能力而发挥作用。KEYTRUDA 是一种人源化单克隆抗体，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，可能影响肿瘤细胞和健康细胞。

Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 2,800 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.

默克拥有业内最大的免疫肿瘤学临床研究项目。目前有超过 2800 项试验正在研究 KEYTRUDA，涵盖多种癌症和治疗环境。KEYTRUDA 临床项目旨在了解 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 KEYTRUDA®（帕博利珠单抗）适应症精选

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 与培美曲塞和铂类化疗联合使用，适用于无 EGFR 或 ALK 基因组肿瘤异常的转移性非鳞状非小细胞肺癌（NSCLC）患者的一线治疗。

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 与卡铂和紫杉醇或紫杉醇蛋白结合药物联合使用，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-authorized test, with no EGFR or ALK genomic tumor aberrations, and is:

KEYTRUDA 作为单一药物，适用于 NSCLC 患者的一线治疗，肿瘤表达 PD-L1 [肿瘤比例评分（TPS）≥1%]，由 FDA 授权的检测确定，且无 EGFR 或 ALK 基因组肿瘤异常，且为：

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

III 期，患者不适合手术切除或确切的化学放疗，或
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-authorized 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，适用于转移性 NSCLC 患者的治疗，肿瘤表达 PD-L1（TPS ≥1%），由 FDA 授权的检测确定，且在铂类化疗后疾病进展。具有 EGFR 或 ALK 基因组肿瘤异常的患者应在接受 KEYTRUDA 之前，经历 FDA 批准的针对这些异常的治疗后疾病进展。

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）NSCLC 患者的治疗，联合铂类化疗作为新辅助治疗，手术后继续作为单一药物的辅助治疗。

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，适用于切除后和铂类化疗后的辅助治疗，适用于 IB 期（T2a ≥4 厘米）、II 期或 IIIA 期 NSCLC 的成人患者。

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

请参阅美国其他选择的 KEYTRUDA 适应症，位于重要安全信息之后。

Selected Important Safety Information for KEYTRUDA

KEYTRUDA 的重要安全信息精选

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. 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.

KEYTRUDA 是一种单克隆抗体，属于一类药物，这些药物与程序性死亡受体-1（PD-1）或程序性死亡配体 1（PD-L1）结合，阻断 PD-1/PD-L1 通路，从而消除免疫反应的抑制，可能打破外周耐受性并诱发免疫介导的不良反应。免疫介导的不良反应可能是严重的或致命的，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随时发生。这里列出的重要免疫介导的不良反应可能并不包括所有可能的严重和致命的免疫介导不良反应。

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. 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.

密切监测患者是否出现可能是潜在免疫介导不良反应的症状和体征。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。在治疗开始时及治疗期间定期评估肝酶、肌酐和甲状腺功能。对于在新辅助治疗中接受 KEYTRUDA 治疗的 TNBC 患者，在基线、手术前及临床指示时监测血液皮质醇。在怀疑免疫介导不良反应的情况下，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，包括必要时的专科咨询。

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

根据免疫介导不良反应的严重程度，暂停或永久停用 KEYTRUDA。一般来说，如果 KEYTRUDA 需要中断或停用，给予系统性皮质类固醇治疗（1 至 2 mg/kg/天的泼尼松或等效药物），直到改善至 1 级或更低。改善至 1 级或更低后，开始减少皮质类固醇剂量，并在至少 1 个月内继续减少。对于那些不受皮质类固醇治疗控制的患者，考虑给予其他系统性免疫抑制剂。

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. 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.

KEYTRUDA 可能导致免疫介导性肺炎。在接受过胸部放疗的患者中，发生率更高。在接受 KEYTRUDA 治疗的患者中，免疫介导性肺炎发生率为 3.4%（94/2799），包括致命性（0.1%）、4 级（0.3%）、3 级（0.9%）和 2 级（1.3%）反应。67%（63/94）的患者需要使用系统性皮质类固醇。肺炎导致 1.3%（36）的患者永久停用 KEYTRUDA，0.9%（26）的患者暂停使用。所有被暂停的患者在症状改善后重新开始使用 KEYTRUDA；其中 23% 出现复发。94 名患者中有 59% 的肺炎得到缓解。

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

在接受 KEYTRUDA 作为单一药物治疗的成人 cHL 患者中，肺炎发生率为 8%（31/389），其中 3-4 级反应占 2.3%。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）。接受过和未接受过胸部放疗的患者肺炎发生率相似。肺炎导致 5.4%（21）的患者停用 KEYTRUDA。在发生肺炎的患者中，42% 暂停使用 KEYTRUDA，68% 停用 KEYTRUDA，77% 症状得到缓解。

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). 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.

在接受 KEYTRUDA 作为单一药物进行 NSCLC 术后辅助治疗的成人患者中，肺炎发生率为 7%（41/580），包括致命性（0.2%）、4 级（0.3%）和 3 级（1%）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）。肺炎导致 26 名（4.5%）患者停用 KEYTRUDA。在发生肺炎的患者中，54% 暂停使用 KEYTRUDA，63% 停用 KEYTRUDA，71% 症状得到缓解。

Immune-Mediated Colitis

免疫介导性结肠炎

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

KEYTRUDA 可能导致免疫介导性结肠炎，可能表现为腹泻。已报告在皮质类固醇耐药的免疫介导性结肠炎患者中发生巨细胞病毒感染/再激活。在皮质类固醇耐药的结肠炎病例中，考虑重复感染检查以排除其他病因。免疫介导性结肠炎发生在接受 KEYTRUDA 的患者中为 1.7%（48/2799），包括 4 级（<0.1%）、3 级（1.1%）和 2 级（0.4%）反应。69%（33/48）的患者需要使用系统性皮质类固醇；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）的患者暂停使用。所有被暂停的患者在症状改善后重新开始使用 KEYTRUDA；其中 23% 出现复发。48 名患者中有 85% 的结肠炎得到缓解。

Hepatotoxicity and Immune-Mediated Hepatitis

肝毒性和免疫介导性肝炎

KEYTRUDA as a Single Agent

KEYTRUDA 作为单一药物

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. 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.

KEYTRUDA 可能导致免疫介导性肝炎。在接受 KEYTRUDA 的患者中，免疫介导性肝炎发生率为 0.7%（19/2799），包括 4 级（<0.1%）、3 级（0.4%）和 2 级（0.1%）反应。68%（13/19）的患者需要使用系统性皮质类固醇；11% 的患者需要额外的免疫抑制治疗。肝炎导致 0.2%（6）的患者永久停用 KEYTRUDA，0.3%（9）的患者暂停使用。所有被暂停的患者在症状改善后重新开始使用 KEYTRUDA；其中没有患者复发。19 名患者中有 79% 的肝炎得到缓解。

KEYTRUDA With Axitinib

KEYTRUDA 与阿昔替尼联合使用

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

KEYTRUDA 与阿昔替尼联合使用可能导致肝毒性。在治疗开始前及治疗期间定期监测肝酶。考虑与单独使用药物时相比，更频繁地进行监测。对于肝酶升高，暂停使用 KEYTRUDA 和阿昔替尼，并根据需要考虑使用皮质类固醇。在 KEYTRUDA 与阿昔替尼联合使用的情况下，3 级和 4 级的丙氨酸氨基转移酶（ALT）升高（20%）和天冬氨酸氨基转移酶（AST）升高（13%）的发生频率高于单独使用 KEYTRUDA 的情况。59% 的 ALT 升高患者接受了系统性皮质类固醇治疗。在 ALT≥正常上限（ULN）3 倍（2-4 级，n=116）的患者中，94% 的 ALT 恢复至 0-1 级。在 92 名重新挑战 KEYTRUDA（n=3）或阿昔替尼（n=34）作为单一药物或两者联合（n=55）的患者中，观察到 1 名接受 KEYTRUDA 的患者、16 名接受阿昔替尼的患者和 24 名接受两者的患者 ALT≥正常上限 3 倍的复发。所有 ALT≥正常上限 3 倍复发的患者随后均从该事件中恢复。

Immune-Mediated Endocrinopathies

免疫介导的内分泌病

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. 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.

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，开始对症治疗，包括根据临床需要进行激素替代。根据严重程度暂停使用 KEYTRUDA。接受 KEYTRUDA 的患者中，肾上腺功能不全发生率为 0.8%（22/2799），包括 4 级（<0.1%）、3 级（0.3%）和 2 级（0.3%）反应。77%（17/22）的患者需要系统性皮质类固醇治疗；其中大多数患者仍在接受系统性皮质类固醇治疗。肾上腺功能不全导致<0.1%（1）的患者永久停用 KEYTRUDA，0.3%（8）的患者暂停使用。所有被暂停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. 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. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

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，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。根据严重程度暂停或永久停用 KEYTRUDA。接受 KEYTRUDA 的患者中，垂体炎发生率为 0.6%（17/2799），包括 4 级（<0.1%）、3 级（0.3%）和 2 级（0.2%）反应。94%（16/17）的患者需要系统性皮质类固醇治疗；其中大多数患者仍在接受系统性皮质类固醇治疗。垂体炎导致 0.1%（4）的患者永久停用 KEYTRUDA，0.3%（7）的患者暂停使用。所有被暂停的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. 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.

KEYTRUDA 可能导致免疫介导的甲状腺疾病。甲状腺炎可能伴随或不伴随内分泌病。甲状腺功能亢进后可能出现甲状腺功能减退。根据临床需要为甲状腺功能减退开始激素替代或进行甲状腺功能亢进的医学管理。根据严重程度暂停或永久停用 KEYTRUDA。接受 KEYTRUDA 的患者中，甲状腺炎发生率为 0.6%（16/2799），包括 2 级（0.3%）。没有患者停用，但<0.1%（1）的患者暂停使用 KEYTRUDA。

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. 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. 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. 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.

甲状腺功能亢进发生在接受 KEYTRUDA 的患者中为 3.4%（96/2799），包括 3 级（0.1%）和 2 级（0.8%）。这导致<0.1%（2）的患者永久停用 KEYTRUDA，0.3%（7）的患者暂停使用。所有被暂停的患者在症状改善后重新开始使用 KEYTRUDA。甲状腺功能减退发生在接受 KEYTRUDA 的患者中为 8%（237/2799），包括 3 级（0.1%）和 2 级（6.2%）。这导致<0.1%（1）的患者永久停用 KEYTRUDA，0.5%（14）的患者暂停使用。所有被暂停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。在 1185 名 HNSCC 患者中，新的或加重的甲状腺功能减退发生率较高，接受 KEYTRUDA 作为单一药物或与铂和 FU 联合使用的患者中发生率为 16%，包括 3 级（0.3%）的甲状腺功能减退。在 389 名成人 cHL 患者中，新的或加重的甲状腺功能减退发生率较高，接受 KEYTRUDA 作为单一药物的患者中发生率为 17%，包括 1 级（6.2%）和 2 级（10.8%）的甲状腺功能减退。在 580 名切除性 NSCLC 患者中，新的或加重的甲状腺功能亢进发生率较高，接受 KEYTRUDA 作为单一药物作为辅助治疗的患者中发生率为 11%，包括 3 级（0.2%）的甲状腺功能亢进。在 580 名切除性 NSCLC 患者中，新的或加重的甲状腺功能减退发生率较高，接受 KEYTRUDA 作为单一药物作为辅助治疗（KEYNOTE-091）的患者中发生率为 22%，包括 3 级（0.3%）的甲状腺功能减退。

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

1 型糖尿病（DM），可能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. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

监测患者的高血糖或其他糖尿病的迹象和症状。根据临床需要开始胰岛素治疗。根据严重程度暂停使用 KEYTRUDA。1 型糖尿病在接受 KEYTRUDA 的患者中发生率为 0.2%（6/2799）。这导致<0.1%（1）的患者永久停用，<0.1%（1）的患者暂停使用 KEYTRUDA。所有被暂停的患者在症状改善后重新开始使用 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. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Nephritis resolved in 56% of the 9 patients.

KEYTRUDA 可能导致免疫介导的肾炎。免疫介导的肾炎在接受 KEYTRUDA 的患者中发生率为 0.3%（9/2799），包括 4 级（<0.1%）、3 级（0.1%）和 2 级（0.1%）反应。89%（8/9）的患者需要系统性皮质类固醇治疗。肾炎导致 0.1%（3）的患者永久停用 KEYTRUDA，0.1%（3）的患者暂停使用。所有被暂停的患者在症状改善后重新开始使用 KEYTRUDA；其中没有患者复发。9 名患者中的 56% 肾炎得到缓解。

Immune-Mediated Dermatologic Adverse Reactions

免疫介导的皮肤不良反应

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

KEYTRUDA 可能导致免疫介导的皮疹或皮炎。剥脱性皮炎，包括史蒂文斯 - 约翰逊综合症、嗜酸性粒细胞增多症药物皮疹及全身症状，以及毒性表皮坏死松解症，已在抗 PD-1/PD-L1 治疗中发生。局部润肤剂和/或局部类固醇可能足以治疗轻度至中度非剥脱性皮疹。根据严重程度，暂停或永久停用 KEYTRUDA。接受 KEYTRUDA 治疗的患者中，发生免疫介导的皮肤不良反应的比例为 1.4%（38/2799），包括 3 级（1%）和 2 级（0.1%）反应。40%（15/38）的患者需要使用全身类固醇。这些反应导致 0.1%（2 例）患者永久停用 KEYTRUDA，0.6%（16 例）患者暂停使用 KEYTRUDA。所有被暂停的患者在症状改善后重新开始使用 KEYTRUDA；其中 6% 出现复发。这些反应在 38 名患者中有 79% 得到缓解。

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. 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. 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; Other: Myocarditis-Myositis-Myasthenia Gravis (or Myasthenia-Like) Overlap syndrome, reported as the co-occurrence of either two or all three adverse reactions.

在接受 KEYTRUDA 或其他抗 PD-1/PD-L1 治疗的患者中，以下临床显著的免疫介导不良反应发生率低于 1%（除非另有说明）。一些不良反应已报告严重或致命病例。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、重症肌无力综合症/肌无力（包括加重）、吉兰 - 巴雷综合症、神经麻痹、自身免疫性神经病；眼科： 葡萄膜炎、虹膜炎及其他眼部炎症性毒性反应可能发生。一些病例可能与视网膜脱离相关。各种程度的视力障碍，包括失明，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，考虑类似 Vogt-Koyanagi-Harada 综合症，因为这可能需要使用全身类固醇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%）、多发性肌痛；内分泌： 甲状旁腺功能减退；血液/免疫： 溶血性贫血、再生障碍性贫血、吞噬性淋巴组织细胞增生症、全身性炎症反应综合症、组织细胞坏死性淋巴结炎（菊池淋巴结炎）、肉芽肿病、免疫性血小板减少性紫癜、实质器官移植排斥、其他移植（包括角膜移植）排斥；其他：心肌炎 - 肌炎 - 重症肌无力（或类似重症肌无力）重叠综合症，报告为两种或三种不良反应的共现。

Infusion-Related Reactions

输注相关反应

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

KEYTRUDA 可能导致严重或危及生命的输注相关反应，包括过敏反应和过敏性休克，在接受 KEYTRUDA 的 2799 名患者中报告发生率为 0.2%。监测输注相关反应的迹象和症状。对于 1 级或 2 级反应，暂停或减慢输注速度。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). 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.

在接受异基因 HSCT 的患者中，可能发生致命和其他严重并发症，这些患者在抗 PD-1/PD-L1 治疗前或后接受治疗。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、减轻强度条件下的肝静脉阻塞病，以及需要类固醇的发热综合症（无明确感染原因）。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。密切观察患者是否有这些并发症的证据，并及时干预。在异基因 HSCT 前或后使用抗 PD-1/PD-L1 治疗时，考虑其益处与风险。

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 与沙利度胺类似物和地塞米松联合使用导致死亡率增加。在此组合中，不建议在控制试验之外使用抗 PD-1/PD-L1 治疗。

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 在孕妇中使用时可能对胎儿造成伤害。告知女性这一潜在风险。在具有生育潜力的女性中，在开始使用 KEYTRUDA 之前确认怀孕状态，并建议她们在治疗期间及最后一次剂量后 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%). The most common adverse reactions (≥20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

在 KEYNOTE-006 中，因不良反应而停用 KEYTRUDA 的患者占 555 名晚期黑色素瘤患者的 9%；导致超过一名患者永久停用的主要不良反应包括结肠炎（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%）和心脏衰竭（0.4%）。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. 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.

在 KEYNOTE-054 中，当 KEYTRUDA 作为单一药物给药给 III 期黑色素瘤患者时，因不良反应而永久停用 KEYTRUDA 的患者占 509 名患者的 14%；最常见的（≥1%）为肺炎（1.4%）、结肠炎（1.2%）和腹泻（1%）。接受 KEYTRUDA 治疗的患者中，25% 发生严重不良反应。KEYTRUDA 最常见的不良反应（≥20%）为腹泻（28%）。在 KEYNOTE-716 中，当 KEYTRUDA 作为单一药物给药给 IIB 或 IIC 期黑色素瘤患者时，IIB 或 IIC 期黑色素瘤患者的不良反应与 KEYNOTE-054 中 1011 名 III 期黑色素瘤患者的不良反应相似。

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%). 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%).

在 KEYNOTE-189 研究中，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% 因不良反应停用 KEYTRUDA。导致 KEYTRUDA 永久停用的最常见不良反应为肺炎（3%）和急性肾损伤（2%）。与 KEYTRUDA 相关的最常见不良反应（≥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. 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 研究中，当 KEYTRUDA 与卡铂和紫杉醇或紫杉醇蛋白结合物联合用于转移性鳞状非小细胞肺癌时，101 名患者中有 15% 因不良反应停用 KEYTRUDA。至少 2% 的患者报告的最常见严重不良反应为发热性中性粒细胞减少症、肺炎和尿路感染。KEYNOTE-407 中观察到的与 KEYTRUDA 相关的不良反应与 KEYNOTE-189 中观察到的相似，唯一的例外是 KEYTRUDA 和化疗组的脱发发生率（47% 对 36%）和周围神经病（31% 对 25%）有所增加。

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

在 KEYNOTE-042 研究中，KEYTRUDA 因不良反应在 636 名晚期非小细胞肺癌患者中停用的比例为 19%；最常见的不良反应为肺炎（3%）、死因不明（1.6%）和肺炎（1.4%）。至少 2% 的患者报告的最常见严重不良反应为肺炎（7%）、肺炎（3.9%）、肺栓塞（2.4%）和胸腔积液（2.2%）。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，KEYTRUDA 单药治疗在 682 名转移性非小细胞肺癌患者中因不良反应停用的比例为 8%；最常见的不良反应为肺炎（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，接受 KEYTRUDA 与铂类化疗联合治疗的可切除非小细胞肺癌患者的不良反应通常与其他临床试验中接受 KEYTRUDA 与化疗联合治疗的患者相似。

The most common adverse reactions (reported in ≥20%) in patients receiving KEYTRUDA in combination with chemotherapy or chemoradiotherapy 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, hypothyroidism, radiation skin injury, dysphagia, dry mouth, and musculoskeletal pain.

在接受 KEYTRUDA 与化疗或放化疗联合治疗的患者中，最常见的不良反应（≥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、粘膜炎、口腔炎、头痛、体重减轻、腹痛、关节痛、肌肉痛、失眠、掌跖红斑、尿路感染、甲状腺功能减退、放射性皮肤损伤、吞咽困难、口干和肌肉骨骼疼痛。

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%). 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%).

在 KEYNOTE-671 的辅助治疗阶段，当 KEYTRUDA 与铂类化疗联合作为新辅助治疗时，396 名患者中有 34% 出现严重不良反应。最常见的（≥2%）严重不良反应为肺炎（4.8%）、静脉血栓栓塞（3.3%）和贫血（2%）。1.3% 的患者出现致命性不良反应，包括死因不明（0.8%）、脓毒症（0.3%）和免疫介导的肺病（0.3%）。因不良反应导致任何研究药物永久停用的患者占接受 KEYTRUDA 与铂类化疗联合治疗的患者的 18%；导致任何研究药物永久停用的最常见不良反应（≥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% 因不良反应未能接受手术。导致 KEYTRUDA 组手术取消的最常见（≥1%）不良反应为间质性肺病（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 作为单药进行辅助治疗时，290 名患者中有 14% 出现严重不良反应。最常见的严重不良反应为肺炎（3.4%）。发生了一例致命性不良反应，即肺出血。因不良反应导致 KEYTRUDA 永久停用的患者占接受 KEYTRUDA 单药辅助治疗的患者的 12%；导致 KEYTRUDA 永久停用的最常见不良反应（≥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通常与其他接受 KEYTRUDA 单药治疗的非小细胞肺癌患者相似，唯一的例外是甲状腺功能减退（22%）、甲状腺功能亢进（11%）和肺炎（7%）。发生了两例致命性不良反应，即心肌炎。

Adverse reactions observed in KEYNOTE-483 were generally similar to those occurring in other patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy.

在 KEYNOTE-483 中观察到的不良反应通常与其他接受 KEYTRUDA 与培美曲塞和铂类化疗联合治疗的患者相似。

In KEYNOTE-689, the most common adverse reactions (≥20%) in patients receiving KEYTRUDA were stomatitis (48%), radiation skin injury (40%), weight loss (36%), fatigue (33%), dysphagia (29%), constipation (27%), hypothyroidism (26%), nausea (24%), rash (22%), dry mouth (22%), diarrhea (22%), and musculoskeletal pain (22%).

在 KEYNOTE-689 中，接受 KEYTRUDA 的患者中最常见的不良反应（≥20%）包括口腔炎（48%）、放射性皮肤损伤（40%）、体重减轻（36%）、疲劳（33%）、吞咽困难（29%）、便秘（27%）、甲状腺功能减退（26%）、恶心（24%）、皮疹（22%）、口干（22%）、腹泻（22%）和肌肉骨骼疼痛（22%）。

In the neoadjuvant phase of KEYNOTE-689, of the 361 patients who received at least one dose of single agent KEYTRUDA, 11% experienced serious adverse reactions. Serious adverse reactions that occurred in more than one patient were pneumonia (1.4%), tumor hemorrhage (0.8%), dysphagia (0.6%), immune-mediated hepatitis (0.6%), cellulitis (0.6%), and dyspnea (0.6%). Fatal adverse reactions occurred in 1.1% of patients, including respiratory failure, clostridium infection, septic shock, and myocardial infarction (one patient each). Permanent discontinuation of KEYTRUDA due to an adverse reaction occurred in 2.8% of patients who received KEYTRUDA as neoadjuvant treatment. The most frequent adverse reaction which resulted in permanent discontinuation of neoadjuvant KEYTRUDA in more than one patient was arthralgia (0.6%).

在 KEYNOTE-689 的新辅助阶段，361 名接受至少一次单药 KEYTRUDA 治疗的患者中，有 11% 经历了严重不良反应。发生在超过一名患者的严重不良反应包括肺炎（1.4%）、肿瘤出血（0.8%）、吞咽困难（0.6%）、免疫介导的肝炎（0.6%）、蜂窝组织炎（0.6%）和呼吸困难（0.6%）。致命性不良反应发生在 1.1% 的患者中，包括呼吸衰竭、梭状芽孢杆菌感染、脓毒性休克和心肌梗死（各一名患者）。因不良反应而永久停用 KEYTRUDA 的患者占接受 KEYTRUDA 作为新辅助治疗的患者的 2.8%。导致超过一名患者永久停用新辅助 KEYTRUDA 的最常见不良反应是关节痛（0.6%）。

Of the 361 patients who received KEYTRUDA as neoadjuvant treatment, 11% did not receive surgery. Surgical cancellation on the KEYTRUDA arm was due to disease progression in 4%, patient decision in 3%, adverse reactions in 1.4%, physician’s decision in 1.1%, unresectable tumor in 0.6%, loss of follow-up in 0.3%, and use of non-study anti-cancer therapy in 0.3%.

在 361 名接受 KEYTRUDA 作为新辅助治疗的患者中，有 11% 未接受手术。KEYTRUDA 组的手术取消原因包括疾病进展 4%、患者决定 3%、不良反应 1.4%、医生决定 1.1%、肿瘤不可切除 0.6%、失访 0.3% 以及使用非研究抗癌治疗 0.3%。

Of the 323 KEYTRUDA-treated patients who received surgery following the neoadjuvant phase, 1.2% experienced delay of surgery (defined as on-study surgery occurring ≥9 weeks after initiation of neoadjuvant KEYTRUDA) due to adverse reactions, and 2.8% did not receive adjuvant treatment due to adverse reactions.

在 323 名接受 KEYTRUDA 治疗并在新辅助阶段后接受手术的患者中，有 1.2% 因不良反应经历了手术延迟（定义为在新辅助 KEYTRUDA 开始后≥9 周进行的研究内手术），2.8% 因不良反应未接受辅助治疗。

In the adjuvant phase of KEYNOTE-689, of the 255 patients who received at least one dose of KEYTRUDA, 38% experienced serious adverse reactions. The most frequent serious adverse reactions reported in ≥1% of KEYTRUDA- treated patients were pneumonia (2.7%), pyrexia (2.4%), stomatitis (2.4%), acute kidney injury (2.0%), pneumonitis (1.6%), COVID-19 (1.2%), death not otherwise specified (1.2%), diarrhea (1.2%), dysphagia (1.2%), gastrostomy tube site complication (1.2%), and immune-mediated hepatitis (1.2%). Fatal adverse reactions occurred in 5% of patients, including death not otherwise specified (1.2%), acute renal failure (0.4%), hypercalcemia (0.4%), pulmonary hemorrhage (0.4%), dysphagia/malnutrition (0.4%), mesenteric thrombosis (0.4%), sepsis (0.4%), pneumonia (0.4%), COVID-19 (0.4%), respiratory failure (0.4%), cardiovascular disorder (0.4%), and gastrointestinal hemorrhage (0.4%). Permanent discontinuation of adjuvant KEYTRUDA due to an adverse reaction occurred in 17% of patients. The most frequent (≥1%) adverse reactions that led to permanent discontinuation of adjuvant KEYTRUDA were pneumonitis, colitis, immune-mediated hepatitis, and death not otherwise specified.

在 KEYNOTE-689 的辅助阶段，255 名接受至少一次 KEYTRUDA 治疗的患者中，有 38% 经历了严重不良反应。报告在≥1% 的 KEYTRUDA 治疗患者中最常见的严重不良反应包括肺炎（2.7%）、发热（2.4%）、口腔炎（2.4%）、急性肾损伤（2.0%）、肺炎（1.6%）、COVID-19（1.2%）、未另行说明的死亡（1.2%）、腹泻（1.2%）、吞咽困难（1.2%）、胃造口管部位并发症（1.2%）和免疫介导的肝炎（1.2%）。致命性不良反应发生在 5% 的患者中，包括未另行说明的死亡（1.2%）、急性肾衰竭（0.4%）、高钙血症（0.4%）、肺出血（0.4%）、吞咽困难/营养不良（0.4%）、肠系膜血栓（0.4%）、脓毒症（0.4%）、肺炎（0.4%）、COVID-19（0.4%）、呼吸衰竭（0.4%）、心血管疾病（0.4%）和胃肠道出血（0.4%）。因不良反应而永久停用辅助 KEYTRUDA 的患者占 17%。导致永久停用辅助 KEYTRUDA 的最常见（≥1%）不良反应包括肺炎、结肠炎、免疫介导的肝炎和未另行说明的死亡。

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 名 HNSCC 患者中有 12% 因不良事件而停用 KEYTRUDA 单药治疗；导致永久停用的最常见不良反应是脓毒症（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%). 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%).

在 KEYNOTE-048 中，当 KEYTRUDA 与铂类（顺铂或卡铂）和氟尿嘧啶化疗联合使用时，276 名 HNSCC 患者中有 16% 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（2.5%）、肺炎（1.8%）和脓毒性休克（1.4%）。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. 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.

在 KEYNOTE-012 中，192 名 HNSCC 患者中有 17% 因不良反应而停用 KEYTRUDA。45% 的患者经历了严重不良反应。至少 2% 的患者中最常见的严重不良反应包括肺炎、呼吸困难、意识混乱、呕吐、胸腔积液和呼吸衰竭。最常见的不良反应（≥20%）是疲劳、食欲减退和呼吸困难。HNSCC 患者的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患者相似，唯一的例外是面部水肿和新发或加重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. 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).

在 KEYNOTE-204 中，148 名 cHL 患者中有 14% 因不良反应而停用 KEYTRUDA。接受 KEYTRUDA 的患者中有 30% 经历了严重不良反应；≥1% 的不良反应包括肺炎、肺炎、发热、心肌炎、急性肾损伤、发热性中性粒细胞减少症和脓毒症。有三名患者因非疾病进展原因死亡：2 名因异体造血干细胞移植后并发症，1 名因未知原因。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%）以及发热、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. The most common adverse reactions (≥20%) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

在 KEYNOTE-087 中，210 名 cHL 患者中有 5% 因不良反应而停用 KEYTRUDA。16% 的患者经历了严重不良反应；≥1% 的不良反应包括肺炎、肺炎、发热、呼吸困难、GVHD 和带状疱疹。有两名患者因非疾病进展原因死亡：1 名因后续异体造血干细胞移植后的 GVHD，1 名因脓毒性休克。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. 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%).

在 KEYNOTE-170 中，53 名 PMBCL 患者中有 8% 因不良反应而停用 KEYTRUDA。26% 的患者经历了严重不良反应，包括心律失常（4%）、心包压塞（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。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%). 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%). 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%).

在 KEYNOTE-A39 研究中，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，发生致命不良反应的比例为 3.9%，包括急性呼吸衰竭（0.7%）、肺炎（0.5%）和肺炎/间质性肺病（0.2%）。接受 KEYTRUDA 与 enfortumab vedotin 联合治疗的患者中，有 50% 出现严重不良反应；其中≥2% 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%）。由于不良反应，27% 的患者永久停用 KEYTRUDA。导致 KEYTRUDA 永久停用的最常见不良反应（≥2%）为肺炎/间质性肺病（4.8%）和皮疹（3.4%）。在接受 KEYTRUDA 与 enfortumab vedotin 联合治疗的患者中，发生的最常见不良反应（≥20%）为皮疹（68%）、周围神经病（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（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. The most common adverse reactions (≥20%) were fatigue (38%), musculoskeletal pain (24%), decreased appetite (22%), constipation (21%), rash (21%), and diarrhea (20%).

在 KEYNOTE-052 研究中，由于不良反应，370 名局部晚期或转移性尿路上皮癌患者中有 11% 停用 KEYTRUDA。42% 的患者出现严重不良反应；其中≥2% 的包括尿路感染、血尿、急性肾损伤、肺炎和尿源性败血症。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. 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%).

在 KEYNOTE-045 研究中，由于不良反应，266 名局部晚期或转移性尿路上皮癌患者中有 8% 停用 KEYTRUDA。导致 KEYTRUDA 永久停用的最常见不良反应为肺炎（1.9%）。39% 的 KEYTRUDA 治疗患者出现严重不良反应；其中≥2% 的包括尿路感染、肺炎、贫血和肺炎。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-905, the most common adverse reactions (≥20%) occurring in cisplatin-ineligible patients with MIBC treated with KEYTRUDA in combination with enfortumab vedotin (n=167) were rash (54%), pruritus (47%), fatigue (47%), peripheral neuropathy (39%), alopecia (35%), dysgeusia (35%), diarrhea (34%), constipation (28%), decreased appetite (28%), nausea (26%), urinary tract infection (24%), dry eye (21%), and weight loss (20%).

在 KEYNOTE-905 研究中，接受 KEYTRUDA 与 enfortumab vedotin 联合治疗的 MIBC 患者（n=167）中，发生的最常见不良反应（≥20%）为皮疹（54%）、瘙痒（47%）、疲劳（47%）、周围神经病（39%）、脱发（35%）、味觉障碍（35%）、腹泻（34%）、便秘（28%）、食欲减退（28%）、恶心（26%）、尿路感染（24%）、干眼（21%）和体重减轻（20%）。

In the neoadjuvant phase of KEYNOTE-905, serious adverse reactions occurred in 27% (n=167) of patients; the most frequent (≥2%) were urinary tract infection (3.6%) and hematuria (2.4%). Fatal adverse reactions occurred in 1.2% of patients, including myasthenia gravis and toxic epidermal necrolysis (0.6% each). Additional fatal adverse reactions were reported in 2.7% of patients in the post-surgery phase before adjuvant treatment started, including sepsis and intestinal obstruction (1.4% each). Permanent discontinuation of KEYTRUDA due to an adverse reaction occurred in 15% of patients; the most frequent (>1%) were rash (2.4%, including generalized exfoliative dermatitis), increased alanine aminotransferase, increased aspartate aminotransferase, diarrhea, dysgeusia, and toxic epidermal necrolysis (1.2% each). Of the 167 patients in the KEYTRUDA in combination with enfortumab vedotin arm who received neoadjuvant treatment, 7 (4.2%) patients did not receive surgery due to adverse reactions. The adverse reactions that led to cancellation of surgery were acute myocardial infarction, bile duct cancer, colon cancer, respiratory distress, urinary tract infection, and the two deaths due to myasthenia gravis and toxic epidermal necrolysis (0.6% each).

在 KEYNOTE-905 的辅助治疗阶段，27% 的患者（n=167）出现严重不良反应；最常见的（≥2%）为尿路感染（3.6%）和血尿（2.4%）。致命不良反应发生在 1.2% 的患者中，包括重症肌无力和毒性表皮坏死松解症（各 0.6%）。在辅助治疗开始前的手术后阶段，2.7% 的患者报告了额外的致命不良反应，包括脓毒症和肠梗阻（各 1.4%）。由于不良反应，15% 的患者永久停用 KEYTRUDA；最常见的（>1%）为皮疹（2.4%，包括广泛性剥脱性皮炎）、丙氨酸氨基转移酶升高、天冬氨酸氨基转移酶升高、腹泻、味觉障碍和毒性表皮坏死松解症（各 1.2%）。在接受 KEYTRUDA 与 enfortumab vedotin 联合治疗的 167 名患者中，有 7 名（4.2%）因不良反应未能接受手术。导致手术取消的不良反应包括急性心肌梗死、胆管癌、结肠癌、呼吸窘迫、尿路感染，以及因重症肌无力和毒性表皮坏死松解症导致的两例死亡（各 0.6%）。

Of the 146 patients who received neoadjuvant treatment with KEYTRUDA in combination with enfortumab vedotin and underwent radical cystectomy, 6 (4.1%) patients experienced delay of surgery (defined as time from last neoadjuvant treatment to surgery exceeding 8 weeks) due to adverse reactions.

在接受 KEYTRUDA 与 enfortumab vedotin 联合治疗并进行根治性膀胱切除术的 146 名患者中，有 6 名（4.1%）因不良反应经历手术延迟（定义为最后一次辅助治疗到手术的时间超过 8 周）。

In the adjuvant phase of KEYNOTE-905, serious adverse reactions occurred in 43% (n=100) of patients; the most frequent (≥2%) were urinary tract infection (8%); acute kidney injury and pyelonephritis (5% each); urosepsis (4%); and hypokalemia, intestinal obstruction, and sepsis (2% each). Fatal adverse reactions occurred in 7% of patients, including urosepsis, intracranial hemorrhage, death, myocardial infarction, multiple organ dysfunction syndrome, and pseudomonal pneumonia (1% each). Permanent discontinuation of KEYTRUDA due to an adverse reaction occurred in 28% of patients; the most frequent (>1%) were diarrhea (5%), peripheral neuropathy, acute kidney injury, and pneumonitis (2% each).

在 KEYNOTE-905 的辅助治疗阶段，43% 的患者（n=100）出现严重不良反应；最常见的（≥2%）为尿路感染（8%）；急性肾损伤和肾盂肾炎（各 5%）；尿源性败血症（4%）；以及低钾血症、肠梗阻和脓毒症（各 2%）。7% 的患者发生致命不良反应，包括尿源性败血症、颅内出血、死亡、心肌梗死、多脏器功能障碍综合征和假单胞菌肺炎（各 1%）。由于不良反应，28% 的患者永久停用 KEYTRUDA；最常见的（>1%）为腹泻（5%）、周围神经病、急性肾损伤和肺炎（各 2%）。

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

在 KEYNOTE-057 研究中，由于不良反应，148 名高风险 NMIBC 患者中有 11% 停用 KEYTRUDA。导致 KEYTRUDA 永久停用的最常见不良反应为肺炎（1.4%）。28% 的患者出现严重不良反应；其中≥2% 的包括肺炎（3%）、心脏缺血（2%）、结肠炎（2%）、肺栓塞（2%）、脓毒症（2%）和尿路感染（2%）。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.

在接受 KEYTRUDA 单药治疗的 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非小细胞肺癌患者相似。

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，发生在 MSI-H 或 dMMR 癌症患者中的不良反应与接受 KEYTRUDA 单药治疗的其他实体瘤患者相似。

In KEYNOTE-811, fatal adverse reactions occurred in 3 patients who received KEYTRUDA in combination with trastuzumab and CAPOX (capecitabine plus oxaliplatin) or FP (5-FU plus cisplatin) 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. 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%).

在 KEYNOTE-811 研究中，接受 KEYTRUDA 与曲妥珠单抗和 CAPOX（卡培他滨加奥沙利铂）或 FP（5-FU 加顺铂）联合治疗的 3 名患者发生了致命的不良反应，其中 2 名患者出现肺炎，1 名患者出现肝炎。在 350 名局部晚期不可切除或转移性 HER2 阳性胃癌或 GEJ 腺癌患者中，因不良反应停用 KEYTRUDA 的比例为 13%。导致 KEYTRUDA 永久停用的≥1% 患者的不良反应包括肺炎（2.0%）和肺炎（1.1%）。在 KEYTRUDA 组与安慰剂组相比，接受 KEYTRUDA 治疗的患者在腹泻（53% vs 47%）、皮疹（35% vs 28%）、甲状腺功能减退（11% vs 5%）和肺炎（11% vs 5%）方面的发生率差异≥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%). 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%). 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%).

在 KEYNOTE-859 研究中，当 KEYTRUDA 与含氟嘧啶和铂类化疗联合使用时，785 名患者中有 45% 发生了严重不良反应。发生率超过 2% 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%）。在接受 KEYTRUDA 的患者中，8% 发生了致命的不良反应，包括感染（2.3%）和血栓栓塞（1.3%）。因不良反应永久停用 KEYTRUDA 的患者比例为 15%。导致 KEYTRUDA 永久停用的最常见不良反应（≥1%）为感染（1.8%）和腹泻（1.0%）。在接受 KEYTRUDA 与化疗联合治疗的患者中，最常见的不良反应（发生率≥20%）为周围神经病（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. 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%).

在 KEYNOTE-590 研究中，当 KEYTRUDA 与顺铂和氟尿嘧啶联合用于不适合手术切除或确切化疗放疗的转移性或局部晚期食管癌或 GEJ（肿瘤中心距 GEJ 1 至 5 厘米）患者时，370 名患者中有 15% 因不良反应停用 KEYTRUDA。导致 KEYTRUDA 永久停用的最常见不良反应（≥1%）为肺炎（1.6%）、急性肾损伤（1.1%）和肺炎（1.1%）。与化疗联合使用 KEYTRUDA 的最常见不良反应（≥20%）为恶心（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 294 patients, including 1 case each (0.3%) of large intestinal perforation, urosepsis, sepsis, and vaginal hemorrhage. Serious adverse reactions occurred in 34% of patients; those ≥1% included urinary tract infection (3.1%), urosepsis (1.4%), and sepsis (1%). KEYTRUDA was discontinued for adverse reactions in 9% of patients. The most common adverse reaction (≥1%) resulting in permanent discontinuation was diarrhea (1%). For patients treated with KEYTRUDA in combination with CRT, the most common adverse reactions (≥10%) were nausea (56%), diarrhea (51%), urinary tract infection (35%), vomiting (34%), fatigue (28%), hypothyroidism (23%), constipation (20%), weight loss (19%), decreased appetite (18%), pyrexia (14%), abdominal pain and hyperthyroidism (13% each), dysuria and rash (12% each), back and pelvic pain (11% each), and COVID-19 (10%).

在 KEYNOTE-A18 研究中，当 KEYTRUDA 与 CRT（顺铂加外照射放疗 [EBRT] 后接种内放射治疗 [BT]）联合用于 FIGO 2014 III-IVA 期宫颈癌患者时，294 名患者中有 1.4% 发生了致命的不良反应，包括 1 例（0.3%）的大肠穿孔、尿源性败血症、脓毒症和阴道出血。34% 的患者发生了严重不良反应；其中≥1% 的包括尿路感染（3.1%）、尿源性败血症（1.4%）和脓毒症（1%）。因不良反应停用 KEYTRUDA 的患者比例为 9%。导致 KEYTRUDA 永久停用的最常见不良反应（≥1%）为腹泻（1%）。对于接受 KEYTRUDA 与 CRT 联合治疗的患者，最常见的不良反应（≥10%）为恶心（56%）、腹泻（51%）、尿路感染（35%）、呕吐（34%）、疲劳（28%）、甲状腺功能减退（23%）、便秘（20%）、体重减轻（19%）、食欲减退（18%）、发热（14%）、腹痛和甲状腺功能亢进（各 13%）、排尿困难和皮疹（各 12%）、背痛和盆腔痛（各 11%）以及 COVID-19（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. 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).

在 KEYNOTE-826 研究中，当 KEYTRUDA 与紫杉醇和顺铂或紫杉醇和卡铂联合使用，是否伴随贝伐单抗（n=307），用于持续、复发或一线转移性宫颈癌患者，无论肿瘤 PD-L1 表达如何，且未接受过化疗（除非作为放射增敏剂同时使用），4.6% 的患者发生了致命的不良反应，包括 3 例出血、2 例脓毒症和未知原因的病例，以及 1 例急性心肌梗死、自身免疫性脑炎、心脏骤停、脑血管意外、股骨骨折伴围手术期肺栓塞、肠穿孔和盆腔感染。接受 KEYTRUDA 与化疗联合治疗的患者中，50% 发生了严重不良反应；其中≥3% 的包括发热性中性粒细胞减少症（6.8%）、尿路感染（5.2%）、贫血（4.6%）和急性肾损伤及脓毒症（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%).

因不良反应停用 KEYTRUDA 的患者比例为 15%。导致 KEYTRUDA 永久停用的最常见不良反应（≥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（62%）、脱发（58%）、贫血（55%）、疲劳/虚弱（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%）和食欲减退（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 与化疗联合治疗（有或没有贝伐单抗）的患者，最常见的不良反应（≥20%）为周围神经病（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). The most common adverse reactions (≥20%) were fatigue (43%), musculoskeletal pain (27%), diarrhea (23%), pain and abdominal pain (22% each), and decreased appetite (21%).

在 KEYNOTE-158 研究中，KEYTRUDA 因不良反应在 98 名接受过治疗的复发性或转移性宫颈癌患者中停用，比例为 8%。接受 KEYTRUDA 的患者中，39% 出现严重不良反应；最常见的不良反应包括贫血（7%）、瘘管、出血和感染（尿路感染除外，均为 4.1%）。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（均为 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 研究中，KEYTRUDA 因不良反应在 299 名接受过治疗的肝细胞癌患者中停用，比例为 13%。导致 KEYTRUDA 永久停用的最常见不良反应为腹水（2.3%）。接受 KEYTRUDA 的患者中，最常见的不良反应（≥10%）为发热（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%). 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%).

在 KEYNOTE-966 研究中，当 KEYTRUDA 与吉西他滨和顺铂联合使用时，KEYTRUDA 因不良反应在 529 名局部晚期不可切除或转移性胆道癌患者中停用，比例为 15%。导致 KEYTRUDA 永久停用的最常见不良反应（≥1%）为肺炎（1.3%）。导致 KEYTRUDA 中断的不良反应发生在 55% 的患者中。导致 KEYTRUDA 中断的最常见不良反应或实验室异常（≥2%）为中性粒细胞减少（18%）、血小板减少（10%）、贫血（6%）、白细胞减少（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，发生在 MCC 患者（n=105）中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%). 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%).

在 KEYNOTE-426 研究中，当 KEYTRUDA 与阿昔替尼联合使用时，429 名患者中发生致命不良反应的比例为 3.3%。40% 的患者出现严重不良反应，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%）。因不良反应永久停用 KEYTRUDA 的患者占 31%；KEYTRUDA 单独（13%）、阿昔替尼单独（13%）和联合治疗（8%）；最常见的为肝毒性（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%）为腹泻（56%）、疲劳/虚弱（52%）、高血压（48%）、肝毒性（39%）、甲状腺功能减退（35%）、食欲减退（30%）、掌跖红斑（28%）、恶心（28%）、口腔炎/黏膜炎（27%）、发音障碍（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). 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%).

在 KEYNOTE-564 研究中，当 KEYTRUDA 作为单药用于肾细胞癌的辅助治疗时，接受 KEYTRUDA 的患者中发生严重不良反应的比例为 20%；严重不良反应（≥1%）包括急性肾损伤、肾上腺功能不全、肺炎、结肠炎和糖尿病酮症酸中毒（各 1%）。发生致命不良反应的比例为 0.2%，包括 1 例肺炎。因不良反应停用 KEYTRUDA 的患者占 488 名患者的 21%；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%）为肌肉骨骼疼痛（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). 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).

在 KEYNOTE-868 研究中，当 KEYTRUDA 与化疗（紫杉醇和卡铂）联合用于 382 名晚期或复发性子宫内膜癌患者时，接受 KEYTRUDA 与化疗联合治疗的患者中发生严重不良反应的比例为 35%，而接受安慰剂与化疗联合治疗的患者中为 19%（n=377）。接受 KEYTRUDA 与化疗联合治疗的患者中发生致命不良反应的比例为 1.6%，包括 COVID-19（0.5%）和心脏骤停（0.3%）。因不良反应停用 KEYTRUDA 的患者占 14%。接受 KEYTRUDA 与化疗联合治疗的患者中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，唯一的例外是皮疹（33% 所有级别；3-4 级为 2.9%）。

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.

接受 KEYTRUDA 单药治疗的 TMB-H 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.

接受 KEYTRUDA 单药治疗的复发性或转移性 cSCC 或局部晚期 cSCC 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. 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%). The most common adverse reactions (≥20%) in patients receiving KEYTRUDA with chemotherapy followed by KEYTRUDA alone 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%).

在 KEYNOTE-522 研究中，当 KEYTRUDA 与新辅助化疗（卡铂和紫杉醇，随后为多柔比星或表柔比星和环磷酰胺）联合使用，并在手术后继续单药 KEYTRUDA 的辅助治疗（n=778）时，针对新诊断的、未接受过治疗的高风险早期三阴性乳腺癌患者，发生致命不良反应的比例为 0.9%，包括与多脏器功能障碍综合征和心肌梗死相关的肾上腺危机、自身免疫性脑炎、肝炎、肺炎、肺炎、肺栓塞和脓毒症各 1 例。接受 KEYTRUDA 治疗的患者中，44% 发生严重不良反应；其中≥2% 的反应包括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% 的患者停止使用 KEYTRUDA。导致永久停药的最常见反应（≥1%）为 ALT 升高（2.7%）、AST 升高（1.5%）和皮疹（1%）。接受 KEYTRUDA 与化疗联合治疗后再单独使用 KEYTRUDA 的患者中，最常见的不良反应（≥20%）为疲劳（70%）、恶心（67%）、脱发（61%）、皮疹（52%）、便秘（42%）、腹泻和周围神经病（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%）和肌肉疼痛（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%). 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%). 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%).

在 KEYNOTE-355 研究中，当 KEYTRUDA 与化疗（紫杉醇、紫杉醇蛋白结合或吉西他滨和卡铂）联合使用于未曾接受过化疗的局部复发不可切除或转移性三阴性乳腺癌患者（n=596）时，发生致命不良反应的比例为 2.5%，包括心肺骤停（0.7%）和脓毒性休克（0.3%）。接受 KEYTRUDA 与化疗联合治疗的患者中，30% 发生严重不良反应；其中≥2% 的严重反应包括肺炎（2.9%）、贫血（2.2%）和血小板减少症（2%）。由于不良反应，11% 的患者停止使用 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%）。接受 KEYTRUDA 与化疗联合治疗的患者中，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%）和头痛（20%）。

In KEYNOTE-B96, when KEYTRUDA was administered in combination with paclitaxel, with or without bevacizumab, serious adverse reactions occurred in 54% of patients. Serious adverse reactions in ≥2% of patients were pneumonia (4.3%), urinary tract infection (3.9%), adrenal insufficiency (3%), hyponatremia (3%), COVID-19, decreased neutrophil count, pulmonary embolism (2.6% each), abdominal pain, anemia, colitis, diarrhea, febrile neutropenia, pyrexia, and vomiting (2.1% each).

在 KEYNOTE-B96 研究中，当 KEYTRUDA 与紫杉醇联合使用（有或没有贝伐单抗）时，54% 的患者发生了严重不良反应。≥2% 的患者中发生的严重不良反应包括肺炎（4.3%）、尿路感染（3.9%）、肾上腺功能不全（3%）、低钠血症（3%）、COVID-19、白细胞减少、肺栓塞（各 2.6%）、腹痛、贫血、结肠炎、腹泻、发热性中性粒细胞减少症、发热和呕吐（各 2.1%）。

Fatal adverse reactions occurred in 3.9% of patients receiving KEYTRUDA and paclitaxel, with or without bevacizumab, including assisted suicide (0.9%), death, intestinal perforation, sepsis, COVID-19, cardio-respiratory arrest, colitis, and embolic stroke (0.4% each).

接受 KEYTRUDA 与紫杉醇联合治疗（有或没有贝伐单抗）的患者中，发生致命不良反应的比例为 3.9%，包括协助自杀（0.9%）、死亡、肠穿孔、脓毒症、COVID-19、心肺骤停、结肠炎和栓塞性中风（各 0.4%）。

KEYTRUDA was permanently discontinued for adverse reactions in 16% of patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA (≥1%) were colitis and increased alanine aminotransferase (1.3% each). Adverse reactions leading to the interruption of KEYTRUDA occurred in 44% of patients. The most common adverse reactions leading to interruption of KEYTRUDA in ≥2% were urinary tract infection (3.9%), adrenal insufficiency, pyrexia, pneumonitis, upper respiratory tract infection (2.6% each), neutropenia, diarrhea, and COVID-19 (2.1% each).

由于不良反应，16% 的患者永久停用 KEYTRUDA。导致 KEYTRUDA 永久停药的最常见不良反应（≥1%）为结肠炎和丙氨酸氨基转移酶升高（各 1.3%）。导致 KEYTRUDA 中断的反应发生在 44% 的患者中。导致 KEYTRUDA 中断的最常见不良反应（≥2%）为尿路感染（3.9%）、肾上腺功能不全、发热、肺炎、上呼吸道感染（各 2.6%）、中性粒细胞减少症、腹泻和 COVID-19（各 2.1%）。

The most common adverse reactions (≥20%) for patients treated with KEYTRUDA in combination with paclitaxel, with or without bevacizumab, were diarrhea (45%), fatigue (43%), nausea (41%), alopecia, peripheral neuropathy (38% each), epistaxis (31%), urinary tract infection (27%), constipation (25%), abdominal pain, decreased appetite, vomiting (24% each), hypothyroidism (21%), cough, hypertension, and rash (20% each).

接受 KEYTRUDA 与紫杉醇联合治疗（有或没有贝伐单抗）的患者中，最常见的不良反应（≥20%）为腹泻（45%）、疲劳（43%）、恶心（41%）、脱发、周围神经病（各 38%）、鼻出血（31%）、尿路感染（27%）、便秘（25%）、腹痛、食欲减退、呕吐（各 24%）、甲状腺功能减退（21%）、咳嗽、高血压和皮疹（各 20%）。

For patients treated with KEYTRUDA in combination with paclitaxel and bevacizumab (N=169), decreased white blood cell count (27%), stomatitis (22%), and pyrexia (21%) were also reported as adverse reactions.

对于接受 KEYTRUDA 与紫杉醇和贝伐单抗联合治疗的患者（N=169），还报告了白细胞减少（27%）、口腔炎（22%）和发热（21%）作为不良反应。

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.

由于母乳喂养儿童可能出现严重不良反应，建议女性在治疗期间及最后一次给药后 4 个月内不要哺乳。

Pediatric Use

儿童使用

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 名儿童患者（65 名 6 个月至 12 岁以下的儿童和 108 名 12 至 17 岁的儿童）接受了每 3 周 2 mg/kg 的 KEYTRUDA 治疗。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 (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，儿童患者中发生≥10% 更高比例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%）、淋巴细胞减少（13%）和白细胞减少（11%）。

Geriatric Use

老年人使用

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 effectiveness were observed between patients 65 years of age or older and younger patients. 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.

在 564 名接受 KEYTRUDA 与恩福妥单抗联合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。65 岁及以上患者与年轻患者之间的疗效没有明显差异。接受 KEYTRUDA 与恩福妥单抗联合治疗的 75 岁及以上患者发生致命不良反应的比例高于年轻患者。75 岁以下患者的致命不良反应发生率为 4%，而 75 岁及以上患者为 7%。

Of the 167 patients with MIBC treated with KEYTRUDA in combination with enfortumab vedotin, 37% (n=61) were 65-74 years and 46% (n=77) were 75 years or older. 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 12% in patients 75 years or older.

在 167 名接受 KEYTRUDA 与 enfortumab vedotin 联合治疗的 MIBC 患者中，37%（n=61）年龄在 65-74 岁之间，46%（n=77）年龄在 75 岁或以上。75 岁及以上的患者在接受 KEYTRUDA 与 enfortumab vedotin 联合治疗时，出现致命不良反应的发生率高于年轻患者。75 岁以下患者的致命不良反应发生率为 4%，而 75 岁及以上患者的发生率为 12%。

Additional Selected KEYTRUDA Indications in the U.S.

美国 KEYTRUDA 的其他适应症

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 适用于在完全切除后对成人和儿童（12 岁及以上）IIB、IIC 或 III 期黑色素瘤患者进行辅助治疗。

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 与 pemetrexed 和铂类化疗联合使用，适用于不可切除的晚期或转移性恶性胸膜间皮瘤（MPM）成人患者的一线治疗。

Head and Neck Squamous Cell Cancer

头颈部鳞状细胞癌

KEYTRUDA is indicated for the treatment of adult patients with resectable locally advanced head and neck squamous cell carcinoma (HNSCC) whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-authorized test, as a single agent as neoadjuvant treatment, continued as adjuvant treatment in combination with radiotherapy (RT) with or without cisplatin and then as a single agent.

KEYTRUDA 适用于治疗可切除的局部晚期头颈部鳞状细胞癌（HNSCC）成人患者，前提是其肿瘤表达 PD-L1 [综合阳性评分（CPS）≥1]，根据 FDA 授权的检测作为单药新辅助治疗，随后作为辅助治疗与放疗（RT）联合使用，可能包括或不包括顺铂，然后作为单药治疗。

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

KEYTRUDA 与铂类和氟尿嘧啶（FU）联合使用，适用于转移性或不可切除、复发性 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 (CPS ≥1) as determined by an FDA-authorized test.

KEYTRUDA 作为单药，适用于转移性或不可切除、复发性 HNSCC 患者的一线治疗，前提是其肿瘤表达 PD-L1（CPS ≥1），根据 FDA 授权的检测。

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 作为单药，适用于在铂类化疗后病情进展的复发性或转移性 HNSCC 患者的治疗。

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）的成人患者。

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 适用于治疗复发性 cHL 或在两条或更多治疗方案后复发的儿童患者。

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 适用于治疗复发性原发性纵隔大 B 细胞淋巴瘤（PMBCL）的成人和儿童患者，或在两条或更多治疗方案后复发的患者。KEYTRUDA 不推荐用于需要紧急细胞减灭治疗的 PMBCL 患者。

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 联合使用，适用于局部晚期或转移性尿路上皮癌的成人患者。

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

KEYTRUDA 作为单药，适用于局部晚期或转移性尿路上皮癌患者的治疗：

who are not eligible for any platinum-containing chemotherapy, or
who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

不适合任何铂类化疗，或
在铂类化疗期间或之后病情进展，或在新辅助或辅助铂类化疗后 12 个月内病情进展。

KEYTRUDA, in combination with enfortumab vedotin, as neoadjuvant treatment and then continued after cystectomy as adjuvant treatment, is indicated for the treatment of adult patients with muscle invasive bladder cancer (MIBC) who are ineligible for cisplatin-containing chemotherapy.

KEYTRUDA 与 enfortumab vedotin 联合使用，作为新辅助治疗，随后在膀胱切除术后继续作为辅助治疗，适用于不适合顺铂化疗的肌肉浸润性膀胱癌（MIBC）成人患者。

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 作为单药，适用于对巴氏杆菌卡介苗（BCG）无反应的高风险非肌肉浸润性膀胱癌（NMIBC）患者的治疗，这些患者有原位癌（CIS）伴或不伴乳头状肿瘤，且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-authorized 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，前提是根据 FDA 授权的检测，患者在先前治疗后病情进展且没有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-authorized test.

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，前提是根据 FDA 授权的检测。

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-authorized test.

KEYTRUDA 与曲妥珠单抗、氟嘧啶类和铂类化疗联合使用，适用于局部晚期不可切除或转移性 HER2 阳性胃癌或胃食管交界（GEJ）腺癌的成人患者，前提是其肿瘤表达 PD-L1（CPS ≥1），根据 FDA 授权的检测。

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-authorized test.

KEYTRUDA 与氟嘧啶类和铂类化疗联合使用，适用于局部晚期不可切除或转移性 HER2 阴性胃癌或胃食管交界（GEJ）腺癌的成人患者，前提是其肿瘤表达 PD-L1（CPS ≥1），根据 FDA 授权的检测。

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（GEJ）癌症（肿瘤中心距 GEJ 1 至 5 厘米）患者，这些患者不适合外科切除或确切的化学放疗：

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

与铂类和氟嘧啶类化疗联合使用，适用于肿瘤表达 PD-L1（CPS ≥1）的患者，或
作为单药，适用于在一条或多条系统治疗后病情进展的肿瘤为鳞状细胞组织学且表达 PD-L1（CPS ≥10）的患者，前提是根据 FDA 授权的检测。

Cervical Cancer

宫颈癌

KEYTRUDA, in combination with chemoradiotherapy (CRT), is indicated for the treatment of patients with locally advanced cervical cancer involving the lower third of the vagina, with or without extension to pelvic sidewall, or hydronephrosis/non-functioning kidney, or spread to adjacent pelvic organs (FIGO 2014 Stage III-IVA).

KEYTRUDA 与化疗放疗（CRT）联合使用，适用于治疗局部晚期宫颈癌患者，该癌症涉及阴道下三分之一，伴或不伴有向盆腔侧壁的扩展，或肾积水/非功能性肾脏，或扩散至邻近盆腔器官（FIGO 2014 III-IVA 期）。

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-authorized test.

KEYTRUDA 与化疗联合使用，伴或不伴贝伐单抗，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 授权的检测确定。

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-authorized test.

KEYTRUDA 作为单一药物，适用于治疗在化疗后病情进展的复发性或转移性宫颈癌患者，其肿瘤表达 PD-L1（CPS ≥1），由 FDA 授权的检测确定。

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 适用于治疗因乙型肝炎引起的肝细胞癌（HCC）患者，这些患者已接受过除含 PD-1/PD-L1 方案以外的系统治疗。

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使用，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

梅克尔细胞癌

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梅克尔细胞癌（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 与阿昔替尼联合使用，适用于治疗成人晚期肾细胞癌（RCC）的首选治疗。

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 适用于肾细胞癌患者的辅助治疗，这些患者在肾切除术后存在中高风险或高风险复发，或在肾切除术后及转移病灶切除后。

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 与卡铂和紫杉醇联合使用，随后作为单一药物继续使用，适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-authorized 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 MSI-H 或 dMMR 的晚期子宫内膜癌成人患者，这些患者在任何环境下的先前系统治疗后病情进展，且不适合进行治愈性手术或放疗，由 FDA 授权的检测确定。

Tumor Mutational Burden-High Cancer

肿瘤突变负荷高癌症

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-authorized 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 突变/兆碱基（mut/Mb）] 的成人和儿童患者，由 FDA 授权的检测确定，这些患者在先前治疗后病情进展，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.

该适应症在肿瘤反应率和反应持续性基础上获得加速批准。该适应症的持续批准可能取决于在确认性试验中验证和描述临床益处。尚未确定 KEYTRUDA 在 TMB-H 中枢神经系统癌症儿童患者中的安全性和有效性。

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）或局部晚期 cSCC，这些癌症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 适用于治疗高风险早期三阴性乳腺癌（TNBC）患者，联合化疗作为新辅助治疗，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-authorized test.

KEYTRUDA 与化疗联合使用，适用于治疗局部复发不可切除或转移性 TNBC 患者，其肿瘤表达 PD-L1（CPS ≥10），由 FDA 授权的检测确定。

Ovarian Cancer

卵巢癌

KEYTRUDA, in combination with paclitaxel, with or without bevacizumab, is indicated for the treatment of adult patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-authorized test, and who have received one or two prior systemic treatment regimens.

KEYTRUDA 与紫杉醇联合使用，伴或不伴贝伐单抗，适用于治疗铂耐药的上皮卵巢癌、输卵管癌或原发性腹膜癌的成人患者，其肿瘤表达 PD-L1（CPS ≥1），由 FDA 授权的检测确定，且这些患者已接受过一或两种先前的系统治疗方案。

About Gilead and Kite Oncology

关于吉利德和 Kite 肿瘤学

Gilead and Kite Oncology are working to transform how cancer is treated. We are innovating with next-generation therapies, combinations and technologies to deliver improved outcomes for people with cancer. We are purposefully building our oncology portfolio and pipeline to address the greatest gaps in care. From antibody-drug conjugate technologies and small molecules to cell therapy-based approaches, we are creating new possibilities for people with cancer.

吉利德和 Kite 肿瘤学致力于改变癌症的治疗方式。我们正在通过下一代疗法、组合和技术进行创新，以改善癌症患者的治疗结果。我们有意识地构建我们的肿瘤学产品组合和管道，以解决护理中的最大差距。从抗体药物偶联技术和小分子到基于细胞治疗的方法，我们正在为癌症患者创造新的可能性。

About Gilead Sciences

关于吉利德科学

Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, cancer and inflammation. In 2025, Gilead announced a planned $32 billion investment to further strengthen its U.S. footprint to power the next era of discovery, job creation and public health preparedness – while continuing to invest globally to ensure patients everywhere benefit from its scientific innovation. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, Calif.

吉利德科学公司是一家生物制药公司，三十多年来致力于医学突破，目标是为所有人创造一个更健康的世界。该公司致力于推进创新药物，以预防和治疗危及生命的疾病，包括 HIV、病毒性肝炎、COVID-19、癌症和炎症。2025 年，吉利德宣布计划投资 320 亿美元，以进一步增强其在美国的影响力，推动下一个发现、创造就业和公共卫生准备的时代，同时继续在全球范围内投资，以确保各地患者受益于其科学创新。吉利德在全球 35 个国家运营，总部位于加利福尼亚州福斯特城。

Forward Looking Statements

前瞻性声明

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including Gilead’s ability to initiate, progress or complete clinical trials within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing or additional clinical trials, including those involving sacituzumab govitecan-hziy (such as EVOKE-03); uncertainties relating to regulatory applications and related filing and approval timelines, including additional pending and potential applications for sacituzumab govitecan-hziy, and the risk that any regulatory approvals, if granted, may be subject to significant limitations on use or subject to withdrawal or other adverse actions by the applicable regulatory authority; the possibility that Gilead may make a strategic decision to discontinue development of programs for indications that are currently under evaluation, including sacituzumab govitecan-hziy for treatment of metastatic NSCLC, and as a result, these programs may never be commercialized for such indications; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2026, as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation and disclaims any intent to update any such forward-looking statements.

本新闻稿包含 1995 年《私人证券诉讼改革法案》所定义的前瞻性声明，这些声明受到风险、不确定性和其他因素的影响，包括吉利德在当前预期时间内启动、推进或完成临床试验的能力，或根本无法完成，以及正在进行或额外临床试验（包括涉及 sacituzumab govitecan-hziy 的试验，如 EVOKE-03）可能产生的不利结果；与监管申请及相关提交和批准时间表的相关不确定性，包括对 sacituzumab govitecan-hziy 的额外待审和潜在申请，以及任何监管批准（如果获得）可能受到重大使用限制或被相关监管机构撤回或采取其他不利行动的风险；吉利德可能做出战略决定，停止对当前正在评估的适应症（包括用于治疗转移性非小细胞肺癌的 sacituzumab govitecan-hziy）开发项目的开发，因此这些项目可能永远无法商业化；以及任何上述内容所依据的假设。这些风险、不确定性和其他因素在吉利德截至2026年3月31日的季度报告（10-Q 表格）中详细描述，已提交给美国证券交易委员会。这些风险、不确定性和其他因素可能导致实际结果与前瞻性声明中提到的结果存在重大差异。所有非历史事实的声明均可视为前瞻性声明。读者应注意，任何此类前瞻性声明并不保证未来的表现，并涉及风险和不确定性，且应谨慎对待这些前瞻性声明。所有前瞻性声明均基于吉利德当前可获得的信息，吉利德不承担任何更新此类前瞻性声明的义务，并对此不表示任何意图。

Trodelvy, Gilead and the Gilead logo are trademarks of Gilead Sciences, Inc., or its related companies.

Trodelvy、Gilead 及 Gilead 标志是 Gilead Sciences, Inc.或其相关公司的商标。

U.S. Prescribing Information for Trodelvy, including BOXED WARNING, is available at www.gilead.com.

Trodelvy 的美国处方信息，包括 盒装警告，可在 www.gilead.com 获取。

For more information about Gilead, please visit the company’s website at www.gilead.com, follow Gilead on X/Twitter (@Gilead Sciences) and LinkedIn (@Gilead-Sciences).

有关吉利德的更多信息，请访问公司网站 www.gilead.com，关注吉利德的 X/Twitter（@Gilead Sciences）和 LinkedIn（@Gilead-Sciences）。

About Merck

关于默克

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

在默克（在美国和加拿大以外称为 MSD），我们团结一致，围绕我们的使命：我们利用尖端科学的力量，拯救和改善全球人们的生活。130 多年来，我们通过开发重要的药物和疫苗为人类带来了希望。我们渴望成为全球首屈一指的研究密集型生物制药公司——今天，我们处于研究的前沿，提供创新的健康解决方案，推动人类和动物疾病的预防和治疗。我们培养多元和包容的全球劳动力，每天负责任地运营，以实现所有人和社区的安全、可持续和健康的未来。有关更多信息，请访问 www.merck.com，并在 X（前身为 Twitter）、Facebook、Instagram、YouTube 和 LinkedIn 上与我们联系。

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

默克公司（Merck & Co., Inc.）的前瞻性声明，位于美国新泽西州拉威

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. 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.

本新闻稿来自默克公司（Merck & Co., Inc.），位于美国新泽西州拉威（“公司”），包括根据 1995 年《美国私人证券诉讼改革法案》的安全港条款定义的 “前瞻性声明”。这些声明基于公司管理层当前的信念和期望，并受到重大风险和不确定性的影响。对于管道候选者，无法保证这些候选者将获得必要的监管批准或证明其商业成功。如果基础假设不准确或风险或不确定性实现，实际结果可能与前瞻性声明中所述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 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一般行业状况和竞争；一般经济因素，包括利率和汇率波动；制药行业监管和美国及国际医疗立法的影响；全球医疗成本控制的趋势；技术进步、竞争对手获得的新产品和专利；新产品开发中固有的挑战，包括获得监管批准；公司准确预测未来市场条件的能力；制造困难或延误；国际经济的财务不稳定和主权风险；依赖于公司对创新产品的专利和其他保护的有效性；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, 2025 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存在重大差异的其他因素可以在公司截至2025年12月31日的年度报告（10-K 表格）和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）上获取。

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，网址为 http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf 以及 KEYTRUDA 的药物指南，网址为 http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf 。

View source version on businesswire.com: https://www.businesswire.com/news/home/20260608789974/en/

在 businesswire.com 上查看源版本：https://www.businesswire.com/news/home/20260608789974/en/

Gilead Contacts:

吉利德联系方式：

Priscilla White, Media

Priscilla White, 媒体

Public_affairs@gilead.com

Jacquie Ross, Investor

Jacquie Ross, 投资者

investor_relations@gilead.com

Merck Media Contact:

默克媒体联系人：

Julie Cunningham

julie.cunningham@merck.com

Merck Investor Relations Contact:

默克投资者关系联系人：

Steven Graziano

(732) 594-1583

Source: Merck & Co., Inc.

来源：默克公司。

默克和吉利德科学更新了 3 期 KEYNOTE-D46/EVOKE-03 研究的进展 | MRK 股票新闻