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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).

新澤西州拉瓦伊 & 加州福斯特城 --（商業資訊）-- 默克（NYSE: MRK），在美國和加拿大以外稱為 MSD，和吉利德科學公司（Nasdaq: GILD）今天宣佈停止進行第 3 期 KEYNOTE-D46/EVOKE-03 研究，該研究調查吉利德的 Trodelvy®（sacituzumab govitecan-hziy）與默克的抗 PD-1 療法 KEYTRUDA®（pembrolizumab）聯合使用，與 KEYTRUDA 單藥治療相比，在某些之前未接受治療的轉移性非小細胞肺癌患者中進行，該患者的腫瘤表達 PD-L1（腫瘤比例評分 [TPS] ≥50%）。這一決定是基於外部數據監測委員會（eDMC）在審查了無進展生存期（PFS）預設最終分析和總體生存期（OS）中期分析的數據後提出的建議。

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.

觀察到 PFS 有數值改善，但未達到統計學顯著性。在計劃的最終分析中，達到統計學顯著的 OS 的可能性不大。Trodelvy 與 KEYTRUDA 聯合使用的安全性特徵與已知的每種藥物的安全性一致。未發現新的安全信號。這些數據將在未來的醫學會議上進行展示。

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.

監管機構已被告知。默克將通知研究調查員 DMC 的建議，並建議研究中的患者與其醫生討論治療方案。正在進行的 Trodelvy 或默克研究沒有變化。

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.

公司對參與 KEYNOTE-D46/EVOKE-03 研究併為這項重要工作做出貢獻的患者、家庭和醫療專業人員表示感謝。

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

Trodelvy 是吉利德科學公司或其相關公司的註冊商標。

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 的註冊商標，該公司是默克公司（Merck & Co., Inc.）的子公司，位於美國新澤西州拉瓦伊。

About Metastatic Non-Small Cell Lung Cancer

關於轉移性非小細胞肺癌

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.

肺癌是全球最常見的癌症之一，2022 年全球報告的新病例估計為 250 萬例。非小細胞肺癌（NSCLC）約佔肺癌的 80% 至 85%，而這些 NSCLC 患者中近一半是在疾病擴散後才被診斷，此時治療選擇更為有限，長期生存率仍然較低。儘管治療有所進展，轉移性 NSCLC 的 5 年生存率仍低於 10%。雖然免疫療法（無論是否聯合化療）是標準的首選治療方案，但並非對所有人有效，因此需要新的治療選擇。

About KEYNOTE-D46/EVOKE-03

關於 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 研究是一項全球開放標籤隨機第 3 期試驗，由默克贊助，評估 Trodelvy（sacituzumab govitecan-hziy）與 KEYTRUDA（pembrolizumab）聯合使用與 KEYTRUDA 單藥治療在之前未接受治療的轉移性非小細胞肺癌（mNSCLC）患者中的療效和安全性，這些患者的腫瘤表達 PD-L1，腫瘤比例評分（TPS）≥50%，且沒有敏感的 EGFR、ALK 或 ROS1 基因改變。大約 620 名患者在全球研究地點入組。

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 隨機分配，接受 Trodelvy（在 21 天週期的第 1 天和第 8 天靜脈注射 10 mg/kg）加 KEYTRUDA（在 21 天週期的第 1 天靜脈注射 200 mg），或 KEYTRUDA 單藥治療（在 21 天週期的第 1 天靜脈注射 200 mg）。KEYTRUDA 的給藥持續最多 35 個週期，Trodelvy 則持續至疾病進展、死亡、不可接受的毒性或滿足其他治療中斷標準。

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.

該研究的兩個主要終點是通過盲法獨立中央審查（BICR）根據 RECIST v1.1 評估的無進展生存期（PFS）和總體生存期（OS）。次要終點包括客觀緩解率（ORR）、緩解持續時間（DOR）、患者報告結果（PROs）和安全性。有關該研究的更多信息，請訪問 ClinicalTrials.gov：NCT05609968。

About Trodelvy

關於 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）是一種首創的針對 Trop-2 的抗體藥物偶聯物。Trop-2 是一種在多種腫瘤類型中高度表達的細胞表面抗原，包括超過 90% 的乳腺癌和肺癌。Trodelvy 的設計採用了一種專有的可水解連接子，連接到 SN-38，這是一種拓撲異構酶 I 抑制劑。這種獨特的組合通過旁觀者效應向 Trop-2 表達細胞和腫瘤微環境提供強效活性。

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 多個國家獲得批准，用於二線或後續治療的轉移性三陰性乳腺癌（TNBC），並在 50 多個國家用於某些接受過治療的 HR+/HER2-轉移性乳腺癌（mBC）患者。醫療專業人員對 Trodelvy 有良好的經驗，該藥在 60 多個國家的 75,000 多名乳腺癌患者的臨牀試驗和真實世界使用中顯示出普遍一致的結果。

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 目前正在多個正在進行的第 3 期試驗中評估，涉及高 Trop-2 表達的多種腫瘤類型。這些與 Trodelvy 相關的研究，包括單藥治療和與 pembrolizumab 聯合使用，涉及 TNBC 和 HR+/HER2-乳腺癌的早期治療方案——包括在治癒性設置中——以及小細胞肺癌和婦科癌症，其中之前的概念驗證研究已證明了臨牀活性。

Indications for Trodelvy

Trodelvy 的適應症

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）是一種針對 Trop-2 的抗體和拓撲異構酶抑制劑偶聯物，適用於治療成年患者：

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轉移性三陰性乳腺癌（mTNBC），已接受兩種或更多先前的系統治療，其中至少一種用於轉移性疾病。

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轉移性激素受體（HR）陽性、人體表皮生長因子受體 2（HER2）陰性（IHC 0、IHC 1+ 或 IHC 2+/ISH–）乳腺癌患者，已接受基於內分泌的治療和至少兩種額外的系統治療。

U.S. Important safety information FOR TRODELVY

美國 TRODELVY 重要安全信息

BOXED WARNING: NEUTROPENIA AND DIARRHEA

警示框：中性粒細胞減少症和腹瀉

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 可能導致嚴重、危及生命或致命的中性粒細胞減少症。對於絕對中性粒細胞計數低於 1500/mm3 或中性粒細胞減少性發熱的患者，應暫停使用 TRODELVY。在治療期間定期監測血細胞計數。建議對所有有發熱性中性粒細胞減少症風險的患者進行 G-CSF 的初級預防。對發熱性中性粒細胞減少症患者應及時啓動抗感染治療。

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 可能導致嚴重腹瀉。監測腹瀉患者，並根據需要補充液體和電解質。腹瀉發生時，評估感染原因，如果結果為陰性，及時啓動洛哌丁胺。如果發生嚴重腹瀉，應暫停使用 TRODELVY，直到恢復至 ≤ 1 級，並減少後續劑量。

CONTRAINDICATIONS

禁忌症

Severe hypersensitivity reaction to TRODELVY.

對 TRODELVY 的嚴重過敏反應。

WARNINGS AND PRECAUTIONS

警告和注意事項

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.

中性粒細胞減少症： 嚴重、危及生命或致命的中性粒細胞減少症可能在治療的第一個週期就發生，並可能需要調整劑量。接受 TRODELVY 治療的患者中有 64% 發生了中性粒細胞減少症。3-4 級中性粒細胞減少症發生在 49% 的患者中。發熱性中性粒細胞減少症發生在 6% 的患者中。中性粒細胞減少性結腸炎發生在 1.4% 的患者中。建議在所有有發熱性中性粒細胞減少症風險的患者中，從治療的第一個週期開始使用 G-CSF 進行初級預防，包括老年患者、既往有中性粒細胞減少症的患者、表現狀態差、器官功能障礙或多種合併症的患者。在治療期間監測絕對中性粒細胞計數（ANC）。在任何週期的第 1 天 ANC 低於 1500/mm3 或在任何週期的第 8 天低於 1000/mm3 時應暫停使用 TRODELVY。對於中性粒細胞減少性發熱應暫停使用 TRODELVY。用 G-CSF 治療中性粒細胞減少症，並在後續週期中根據臨牀需要或根據 USPI 表 2 的指示進行預防。

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.

腹瀉： 所有接受 TRODELVY 治療的患者中有 64% 發生了腹瀉。3-4 級腹瀉發生在 11% 的患者中。有一名患者在腹瀉後發生腸穿孔。導致脱水和隨後的急性腎損傷的腹瀉發生在所有患者中的 0.7%。對於 3-4 級腹瀉應暫停使用 TRODELVY，並在恢復至 ≤ 1 級時重新開始。發生時，評估感染原因，如果結果為陰性，及時啓動洛哌丁胺，初始劑量為 4 毫克，隨後每次腹瀉 2 毫克，最大每日劑量為 16 毫克。腹瀉緩解後 12 小時停止使用洛哌丁胺。根據臨牀需要，還可以採取其他支持措施（例如，液體和電解質替代）。對治療表現出過度膽鹼能反應的患者可以在後續治療中給予適當的預藥（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.

過敏反應和輸注相關反應： TRODELVY 可能導致嚴重的過敏反應，包括危及生命的過敏性反應。嚴重的體徵和症狀包括心臟驟停、低血壓、喘息、血管神經性水腫、腫脹、肺炎和皮膚反應。給藥後 24 小時內發生的過敏反應在 35% 的患者中出現。3-4 級過敏反應發生在 2% 的患者中。導致永久停用 TRODELVY 的過敏反應發生率為 0.2%。過敏性反應的發生率為 0.2%。建議進行預輸注用藥。應準備好藥物和急救設備以便立即處理此類反應。在每次輸注期間及輸注完成後至少 30 分鐘內密切觀察患者是否出現過敏和輸注相關反應。對於 4 級輸注相關反應應永久停用 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.

噁心和嘔吐： TRODELVY 具有致吐性，可能導致嚴重的噁心和嘔吐。所有接受 TRODELVY 治療的患者中有 64% 發生了噁心，3-4 級噁心發生在 3% 的患者中。35% 的患者發生了嘔吐，3-4 級嘔吐發生在 2% 的患者中。建議使用兩種或三種藥物組合（例如，地塞米松與 5-HT3 受體拮抗劑或 NK1 受體拮抗劑以及其他藥物）進行化療引起的噁心和嘔吐（CINV）的預防。對於 3 級噁心或 3-4 級嘔吐應暫停使用 TRODELVY，並在恢復至 ≤ 1 級時與額外的支持措施一起恢復。根據臨牀需要，還可以使用其他止吐藥和其他支持措施。所有患者應獲得帶有明確説明的帶回家藥物，以預防和治療噁心和嘔吐。

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應風險增加： 同型合子攜帶尿苷二磷酸 - 葡萄糖醛酸轉移酶 1A1（UGT1A1）*28 等位基因的患者中性粒細胞減少症、發熱性中性粒細胞減少症和貧血的風險增加，並可能面臨其他不良反應的風險。UGT1A1*28 同型合子的 3-4 級中性粒細胞減少症發生率為 58%，UGT1A1*28 雜合子的發生率為 49%，野生型等位基因同型合子的發生率為 43%。UGT1A1*28 同型合子的 3-4 級貧血發生率為 21%，UGT1A1*28 雜合子的發生率為 10%，野生型等位基因同型合子的發生率為 9%。密切監測已知 UGT1A1 活性降低的患者的不良反應。根據臨牀評估觀察到的不良反應的發生、持續時間和嚴重程度，決定是否暫停或永久停用 TRODELVY，特別是在出現急性早發或異常嚴重的不良反應時，這可能表明 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 - 胎兒毒性： 根據其作用機制，TRODELVY 在孕婦中使用時可能導致致畸和/或胚胎 - 胎兒致死。TRODELVY 含有基因毒性成分 SN-38，並針對快速分裂的細胞。建議孕婦和具有生育潛力的女性注意對胎兒的潛在風險。在使用 TRODELVY 治療期間及最後一次給藥後 6 個月內，建議具有生育潛力的女性使用有效的避孕措施。建議與具有生育潛力的女性伴侶的男性患者在使用 TRODELVY 治療期間及最後一次給藥後 3 個月內使用有效的避孕措施。

ADVERSE REACTIONS

不良反應

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%).

在匯總的安全人羣中，最常見（≥ 25%）的不良反應包括實驗室異常，白細胞計數減少（84%），中性粒細胞計數減少（75%），血紅蛋白減少（69%），腹瀉（64%），噁心（64%），淋巴細胞計數減少（63%），疲勞（51%），脱髮（45%），便秘（37%），血糖升高（37%），白蛋白減少（35%），嘔吐（35%），食慾減退（30%），肌酐清除率減少（28%），鹼性磷酸酶升高（28%），鎂減少（27%），鉀減少（26%），和鈉減少（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（局部晚期或轉移性三陰性乳腺癌）中，最常見的不良反應（發生率 ≥25%）為疲勞、腹瀉、噁心、脱髮、便秘、嘔吐、腹痛和食慾減退。最常見的嚴重不良反應（SAR）（>1%）為中性粒細胞減少（7%）、腹瀉（4%）和肺炎（3%）。27% 的患者報告了 SAR，5% 的患者因不良反應中止治療。ASCENT 研究中最常見的 3-4 級實驗室異常（發生率 ≥25%）為中性粒細胞、白細胞和淋巴細胞減少。

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（局部晚期或轉移性 HR 陽性、HER2 陰性乳腺癌）中，最常見的不良反應（發生率 ≥25%）為腹瀉、疲勞、噁心、脱髮和便秘。最常見的嚴重不良反應（SAR）（>1%）為腹瀉（5%）、發熱性中性粒細胞減少（4%）、中性粒細胞減少（3%）、腹痛、結腸炎、中性粒細胞減少性結腸炎、肺炎和嘔吐（各 2%）。28% 的患者報告了 SAR，6% 的患者因不良反應中止治療。TROPiCS-02 研究中最常見的 3-4 級實驗室異常（發生率 ≥25%）為中性粒細胞和白細胞減少。

DRUG INTERACTIONS

藥物相互作用

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 抑制劑： 與 UGT1A1 抑制劑同時使用 TRODELVY 可能會增加不良反應的發生率，因為可能會增加 SN-38 的全身暴露。避免與 TRODELVY 同時使用 UGT1A1 抑制劑。

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

UGT1A1 誘導劑： 同時接受 UGT1A1 酶誘導劑的患者可能會減少對 SN-38 的暴露。避免與 TRODELVY 同時使用 UGT1A1 誘導劑。

Please see full Prescribing Information , including BOXED WARNING.

請參閲完整的 處方信息 ，包括警示説明。

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

關於 KEYTRUDA®（帕博利珠單抗）靜脈注射，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 是一種抗程序性死亡受體-1（PD-1）療法，通過增強身體免疫系統檢測和對抗腫瘤細胞的能力而發揮作用。KEYTRUDA 是一種人源化單克隆抗體，阻斷 PD-1 與其配體 PD-L1 和 PD-L2 之間的相互作用，從而激活 T 淋巴細胞，可能影響腫瘤細胞和健康細胞。

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.

默克擁有業內最大的免疫腫瘤學臨牀研究項目。目前有超過 2800 項試驗正在研究 KEYTRUDA，涵蓋多種癌症和治療環境。KEYTRUDA 臨牀項目旨在瞭解 KEYTRUDA 在癌症中的作用以及可能預測患者從 KEYTRUDA 治療中受益的因素，包括探索幾種不同的生物標誌物。

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

美國 KEYTRUDA®（帕博利珠單抗）適應症精選

Non-Small Cell Lung Cancer

非小細胞肺癌

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 與培美曲塞和鉑類化療聯合使用，適用於無 EGFR 或 ALK 基因組腫瘤異常的轉移性非鱗狀非小細胞肺癌（NSCLC）患者的一線治療。

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 與卡鉑和紫杉醇或紫杉醇蛋白結合藥物聯合使用，適用於轉移性鱗狀 NSCLC 患者的一線治療。

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 作為單一藥物，適用於 NSCLC 患者的一線治療，腫瘤表達 PD-L1 [腫瘤比例評分（TPS）≥1%]，由 FDA 授權的檢測確定，且無 EGFR 或 ALK 基因組腫瘤異常，且為：

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

III 期，患者不適合手術切除或確切的化學放療，或
轉移性。

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 作為單一藥物，適用於轉移性 NSCLC 患者的治療，腫瘤表達 PD-L1（TPS ≥1%），由 FDA 授權的檢測確定，且在鉑類化療後疾病進展。具有 EGFR 或 ALK 基因組腫瘤異常的患者應在接受 KEYTRUDA 之前，經歷 FDA 批准的針對這些異常的治療後疾病進展。

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 適用於可切除（腫瘤 ≥4 厘米或淋巴結陽性）NSCLC 患者的治療，聯合鉑類化療作為新輔助治療，手術後繼續作為單一藥物的輔助治療。

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 作為單一藥物，適用於切除後和鉑類化療後的輔助治療，適用於 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.

請參閲美國其他選擇的 KEYTRUDA 適應症，位於重要安全信息之後。

Selected Important Safety Information for KEYTRUDA

KEYTRUDA 的重要安全信息精選

Severe and Fatal Immune-Mediated Adverse Reactions

嚴重和致命的免疫介導不良反應

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 是一種單克隆抗體，屬於一類藥物，這些藥物與程序性死亡受體-1（PD-1）或程序性死亡配體 1（PD-L1）結合，阻斷 PD-1/PD-L1 通路，從而消除免疫反應的抑制，可能打破外周耐受性並誘發免疫介導的不良反應。免疫介導的不良反應可能是嚴重的或致命的，可以發生在任何器官系統或組織中，可以同時影響多個身體系統，並且可以在開始治療後或停止治療後隨時發生。這裏列出的重要免疫介導的不良反應可能並不包括所有可能的嚴重和致命的免疫介導不良反應。

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.

密切監測患者是否出現可能是潛在免疫介導不良反應的症狀和體徵。早期識別和管理對於確保安全使用抗 PD-1/PD-L1 治療至關重要。在治療開始時及治療期間定期評估肝酶、肌酐和甲狀腺功能。對於在新輔助治療中接受 KEYTRUDA 治療的 TNBC 患者，在基線、手術前及臨牀指示時監測血液皮質醇。在懷疑免疫介導不良反應的情況下，啓動適當的檢查以排除其他病因，包括感染。及時進行醫療管理，包括必要時的專科諮詢。

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.

根據免疫介導不良反應的嚴重程度，暫停或永久停用 KEYTRUDA。一般來説，如果 KEYTRUDA 需要中斷或停用，給予系統性皮質類固醇治療（1 至 2 mg/kg/天的潑尼松或等效藥物），直到改善至 1 級或更低。改善至 1 級或更低後，開始減少皮質類固醇劑量，並在至少 1 個月內繼續減少。對於那些不受皮質類固醇治療控制的患者，考慮給予其他系統性免疫抑制劑。

Immune-Mediated Pneumonitis

免疫介導性肺炎

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 可能導致免疫介導性肺炎。在接受過胸部放療的患者中，發生率更高。在接受 KEYTRUDA 治療的患者中，免疫介導性肺炎發生率為 3.4%（94/2799），包括致命性（0.1%）、4 級（0.3%）、3 級（0.9%）和 2 級（1.3%）反應。67%（63/94）的患者需要使用系統性皮質類固醇。肺炎導致 1.3%（36）的患者永久停用 KEYTRUDA，0.9%（26）的患者暫停使用。所有被暫停的患者在症狀改善後重新開始使用 KEYTRUDA；其中 23% 出現復發。94 名患者中有 59% 的肺炎得到緩解。

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 作為單一藥物治療的成人 cHL 患者中，肺炎發生率為 8%（31/389），其中 3-4 級反應占 2.3%。患者接受高劑量皮質類固醇治療的中位持續時間為 10 天（範圍：2 天至 53 個月）。接受過和未接受過胸部放療的患者肺炎發生率相似。肺炎導致 5.4%（21）的患者停用 KEYTRUDA。在發生肺炎的患者中，42% 暫停使用 KEYTRUDA，68% 停用 KEYTRUDA，77% 症狀得到緩解。

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 作為單一藥物進行 NSCLC 術後輔助治療的成人患者中，肺炎發生率為 7%（41/580），包括致命性（0.2%）、4 級（0.3%）和 3 級（1%）不良反應。患者接受高劑量皮質類固醇治療的中位持續時間為 10 天（範圍：1 天至 2.3 個月）。肺炎導致 26 名（4.5%）患者停用 KEYTRUDA。在發生肺炎的患者中，54% 暫停使用 KEYTRUDA，63% 停用 KEYTRUDA，71% 症狀得到緩解。

Immune-Mediated Colitis

免疫介導性結腸炎

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 可能導致免疫介導性結腸炎，可能表現為腹瀉。已報告在皮質類固醇耐藥的免疫介導性結腸炎患者中發生鉅細胞病毒感染/再激活。在皮質類固醇耐藥的結腸炎病例中，考慮重複感染檢查以排除其他病因。免疫介導性結腸炎發生在接受 KEYTRUDA 的患者中為 1.7%（48/2799），包括 4 級（<0.1%）、3 級（1.1%）和 2 級（0.4%）反應。69%（33/48）的患者需要使用系統性皮質類固醇；4.2% 的患者需要額外的免疫抑制治療。結腸炎導致 0.5%（15）的患者永久停用 KEYTRUDA，0.5%（13）的患者暫停使用。所有被暫停的患者在症狀改善後重新開始使用 KEYTRUDA；其中 23% 出現復發。48 名患者中有 85% 的結腸炎得到緩解。

Hepatotoxicity and Immune-Mediated Hepatitis

肝毒性和免疫介導性肝炎

KEYTRUDA as a Single Agent

KEYTRUDA 作為單一藥物

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 可能導致免疫介導性肝炎。在接受 KEYTRUDA 的患者中，免疫介導性肝炎發生率為 0.7%（19/2799），包括 4 級（<0.1%）、3 級（0.4%）和 2 級（0.1%）反應。68%（13/19）的患者需要使用系統性皮質類固醇；11% 的患者需要額外的免疫抑制治療。肝炎導致 0.2%（6）的患者永久停用 KEYTRUDA，0.3%（9）的患者暫停使用。所有被暫停的患者在症狀改善後重新開始使用 KEYTRUDA；其中沒有患者復發。19 名患者中有 79% 的肝炎得到緩解。

KEYTRUDA With Axitinib

KEYTRUDA 與阿昔替尼聯合使用

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 與阿昔替尼聯合使用可能導致肝毒性。在治療開始前及治療期間定期監測肝酶。考慮與單獨使用藥物時相比，更頻繁地進行監測。對於肝酶升高，暫停使用 KEYTRUDA 和阿昔替尼，並根據需要考慮使用皮質類固醇。在 KEYTRUDA 與阿昔替尼聯合使用的情況下，3 級和 4 級的丙氨酸氨基轉移酶（ALT）升高（20%）和天冬氨酸氨基轉移酶（AST）升高（13%）的發生頻率高於單獨使用 KEYTRUDA 的情況。59% 的 ALT 升高患者接受了系統性皮質類固醇治療。在 ALT≥正常上限（ULN）3 倍（2-4 級，n=116）的患者中，94% 的 ALT 恢復至 0-1 級。在 92 名重新挑戰 KEYTRUDA（n=3）或阿昔替尼（n=34）作為單一藥物或兩者聯合（n=55）的患者中，觀察到 1 名接受 KEYTRUDA 的患者、16 名接受阿昔替尼的患者和 24 名接受兩者的患者 ALT≥正常上限 3 倍的復發。所有 ALT≥正常上限 3 倍復發的患者隨後均從該事件中恢復。

Immune-Mediated Endocrinopathies

免疫介導的內分泌病

Adrenal Insufficiency

腎上腺功能不全

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 可能導致原發性或繼發性腎上腺功能不全。對於 2 級或更高級別，開始對症治療，包括根據臨牀需要進行激素替代。根據嚴重程度暫停使用 KEYTRUDA。接受 KEYTRUDA 的患者中，腎上腺功能不全發生率為 0.8%（22/2799），包括 4 級（<0.1%）、3 級（0.3%）和 2 級（0.3%）反應。77%（17/22）的患者需要系統性皮質類固醇治療；其中大多數患者仍在接受系統性皮質類固醇治療。腎上腺功能不全導致<0.1%（1）的患者永久停用 KEYTRUDA，0.3%（8）的患者暫停使用。所有被暫停的患者在症狀改善後重新開始使用 KEYTRUDA。

Hypophysitis

垂體炎

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 可能導致免疫介導的垂體炎。垂體炎可能表現為與腫塊效應相關的急性症狀，如頭痛、畏光或視野缺損。垂體炎可能導致垂體功能減退。根據需要開始激素替代。根據嚴重程度暫停或永久停用 KEYTRUDA。接受 KEYTRUDA 的患者中，垂體炎發生率為 0.6%（17/2799），包括 4 級（<0.1%）、3 級（0.3%）和 2 級（0.2%）反應。94%（16/17）的患者需要系統性皮質類固醇治療；其中大多數患者仍在接受系統性皮質類固醇治療。垂體炎導致 0.1%（4）的患者永久停用 KEYTRUDA，0.3%（7）的患者暫停使用。所有被暫停的患者在症狀改善後重新開始使用 KEYTRUDA。

Thyroid Disorders

甲狀腺疾病

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 可能導致免疫介導的甲狀腺疾病。甲狀腺炎可能伴隨或不伴隨內分泌病。甲狀腺功能亢進後可能出現甲狀腺功能減退。根據臨牀需要為甲狀腺功能減退開始激素替代或進行甲狀腺功能亢進的醫學管理。根據嚴重程度暫停或永久停用 KEYTRUDA。接受 KEYTRUDA 的患者中，甲狀腺炎發生率為 0.6%（16/2799），包括 2 級（0.3%）。沒有患者停用，但<0.1%（1）的患者暫停使用 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.

甲狀腺功能亢進發生在接受 KEYTRUDA 的患者中為 3.4%（96/2799），包括 3 級（0.1%）和 2 級（0.8%）。這導致<0.1%（2）的患者永久停用 KEYTRUDA，0.3%（7）的患者暫停使用。所有被暫停的患者在症狀改善後重新開始使用 KEYTRUDA。甲狀腺功能減退發生在接受 KEYTRUDA 的患者中為 8%（237/2799），包括 3 級（0.1%）和 2 級（6.2%）。這導致<0.1%（1）的患者永久停用 KEYTRUDA，0.5%（14）的患者暫停使用。所有被暫停的患者在症狀改善後重新開始使用 KEYTRUDA。大多數甲狀腺功能減退的患者需要長期的甲狀腺激素替代治療。在 1185 名 HNSCC 患者中，新的或加重的甲狀腺功能減退發生率較高，接受 KEYTRUDA 作為單一藥物或與鉑和 FU 聯合使用的患者中發生率為 16%，包括 3 級（0.3%）的甲狀腺功能減退。在 389 名成人 cHL 患者中，新的或加重的甲狀腺功能減退發生率較高，接受 KEYTRUDA 作為單一藥物的患者中發生率為 17%，包括 1 級（6.2%）和 2 級（10.8%）的甲狀腺功能減退。在 580 名切除性 NSCLC 患者中，新的或加重的甲狀腺功能亢進發生率較高，接受 KEYTRUDA 作為單一藥物作為輔助治療的患者中發生率為 11%，包括 3 級（0.2%）的甲狀腺功能亢進。在 580 名切除性 NSCLC 患者中，新的或加重的甲狀腺功能減退發生率較高，接受 KEYTRUDA 作為單一藥物作為輔助治療（KEYNOTE-091）的患者中發生率為 22%，包括 3 級（0.3%）的甲狀腺功能減退。

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

1 型糖尿病（DM），可能表現為糖尿病酮症酸中毒

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.

監測患者的高血糖或其他糖尿病的跡象和症狀。根據臨牀需要開始胰島素治療。根據嚴重程度暫停使用 KEYTRUDA。1 型糖尿病在接受 KEYTRUDA 的患者中發生率為 0.2%（6/2799）。這導致<0.1%（1）的患者永久停用，<0.1%（1）的患者暫停使用 KEYTRUDA。所有被暫停的患者在症狀改善後重新開始使用 KEYTRUDA。

Immune-Mediated Nephritis With Renal Dysfunction

免疫介導的腎炎伴腎功能障礙

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 可能導致免疫介導的腎炎。免疫介導的腎炎在接受 KEYTRUDA 的患者中發生率為 0.3%（9/2799），包括 4 級（<0.1%）、3 級（0.1%）和 2 級（0.1%）反應。89%（8/9）的患者需要系統性皮質類固醇治療。腎炎導致 0.1%（3）的患者永久停用 KEYTRUDA，0.1%（3）的患者暫停使用。所有被暫停的患者在症狀改善後重新開始使用 KEYTRUDA；其中沒有患者復發。9 名患者中的 56% 腎炎得到緩解。

Immune-Mediated Dermatologic Adverse Reactions

免疫介導的皮膚不良反應

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 可能導致免疫介導的皮疹或皮炎。剝脱性皮炎，包括史蒂文斯 - 約翰遜綜合症、嗜酸性粒細胞增多症藥物皮疹及全身症狀，以及毒性表皮壞死鬆解症，已在抗 PD-1/PD-L1 治療中發生。局部潤膚劑和/或局部類固醇可能足以治療輕度至中度非剝脱性皮疹。根據嚴重程度，暫停或永久停用 KEYTRUDA。接受 KEYTRUDA 治療的患者中，發生免疫介導的皮膚不良反應的比例為 1.4%（38/2799），包括 3 級（1%）和 2 級（0.1%）反應。40%（15/38）的患者需要使用全身類固醇。這些反應導致 0.1%（2 例）患者永久停用 KEYTRUDA，0.6%（16 例）患者暫停使用 KEYTRUDA。所有被暫停的患者在症狀改善後重新開始使用 KEYTRUDA；其中 6% 出現復發。這些反應在 38 名患者中有 79% 得到緩解。

Other Immune-Mediated Adverse Reactions

其他免疫介導的不良反應

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 治療的患者中，以下臨牀顯著的免疫介導不良反應發生率低於 1%（除非另有説明）。一些不良反應已報告嚴重或致命病例。心臟/血管： 心肌炎、心包炎、血管炎；神經系統： 腦膜炎、腦炎、脊髓炎和脱髓鞘、重症肌無力綜合症/肌無力（包括加重）、吉蘭 - 巴雷綜合症、神經麻痹、自身免疫性神經病；眼科： 葡萄膜炎、虹膜炎及其他眼部炎症性毒性反應可能發生。一些病例可能與視網膜脱離相關。各種程度的視力障礙，包括失明，可能發生。如果葡萄膜炎與其他免疫介導的不良反應同時發生，考慮類似 Vogt-Koyanagi-Harada 綜合症，因為這可能需要使用全身類固醇以降低永久性視力喪失的風險；胃腸道： 胰腺炎，包括血清澱粉酶和脂肪酶水平升高、胃炎、十二指腸炎；肌肉骨骼和結締組織： 肌炎/多發性肌炎、橫紋肌溶解症（及相關後遺症，包括腎衰竭）、關節炎（1.5%）、多發性肌痛；內分泌： 甲狀旁腺功能減退；血液/免疫： 溶血性貧血、再生障礙性貧血、吞噬性淋巴組織細胞增生症、全身性炎症反應綜合症、組織細胞壞死性淋巴結炎（菊池淋巴結炎）、肉芽腫病、免疫性血小板減少性紫癜、實質器官移植排斥、其他移植（包括角膜移植）排斥；其他：心肌炎 - 肌炎 - 重症肌無力（或類似重症肌無力）重疊綜合症，報告為兩種或三種不良反應的共現。

Infusion-Related Reactions

輸注相關反應

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 可能導致嚴重或危及生命的輸注相關反應，包括過敏反應和過敏性休克，在接受 KEYTRUDA 的 2799 名患者中報告發生率為 0.2%。監測輸注相關反應的跡象和症狀。對於 1 級或 2 級反應，暫停或減慢輸注速度。對於 3 級或 4 級反應，停止輸注並永久停用 KEYTRUDA。

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

異基因造血幹細胞移植（HSCT）的併發症

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.

在接受異基因 HSCT 的患者中，可能發生致命和其他嚴重併發症，這些患者在抗 PD-1/PD-L1 治療前或後接受治療。移植相關併發症包括超急性移植物抗宿主病（GVHD）、急性和慢性 GVHD、減輕強度條件下的肝靜脈阻塞病，以及需要類固醇的發熱綜合症（無明確感染原因）。這些併發症可能在抗 PD-1/PD-L1 治療與異基因 HSCT 之間的干預治療後仍然發生。密切觀察患者是否有這些併發症的證據，並及時干預。在異基因 HSCT 前或後使用抗 PD-1/PD-L1 治療時，考慮其益處與風險。

Increased Mortality in Patients With Multiple Myeloma

多發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.

在多發性骨髓瘤患者的試驗中，將 KEYTRUDA 與沙利度胺類似物和地塞米松聯合使用導致死亡率增加。在此組合中，不建議在控制試驗之外使用抗 PD-1/PD-L1 治療。

Embryofetal Toxicity

胚胎胎兒毒性

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.

根據其作用機制，KEYTRUDA 在孕婦中使用時可能對胎兒造成傷害。告知女性這一潛在風險。在具有生育潛力的女性中，在開始使用 KEYTRUDA 之前確認懷孕狀態，並建議她們在治療期間及最後一次劑量後 4 個月內使用有效的避孕措施。

Adverse Reactions

不良反應

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，因不良反應而停用 KEYTRUDA 的患者佔 555 名晚期黑色素瘤患者的 9%；導致超過一名患者永久停用的主要不良反應包括結腸炎（1.4%）、自身免疫性肝炎（0.7%）、過敏反應（0.4%）、多發性神經病（0.4%）和心臟衰竭（0.4%）。KEYTRUDA 最常見的不良反應（≥20%）為疲勞（28%）、腹瀉（26%）、皮疹（24%）和噁心（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，當 KEYTRUDA 作為單一藥物給藥給 III 期黑色素瘤患者時，因不良反應而永久停用 KEYTRUDA 的患者佔 509 名患者的 14%；最常見的（≥1%）為肺炎（1.4%）、結腸炎（1.2%）和腹瀉（1%）。接受 KEYTRUDA 治療的患者中，25% 發生嚴重不良反應。KEYTRUDA 最常見的不良反應（≥20%）為腹瀉（28%）。在 KEYNOTE-716 中，當 KEYTRUDA 作為單一藥物給藥給 IIB 或 IIC 期黑色素瘤患者時，IIB 或 IIC 期黑色素瘤患者的不良反應與 KEYNOTE-054 中 1011 名 III 期黑色素瘤患者的不良反應相似。

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，當 KEYTRUDA 與培美曲塞和鉑類化療聯合用於轉移性非鱗狀非小細胞肺癌時，405 名患者中有 20% 因不良反應停用 KEYTRUDA。導致 KEYTRUDA 永久停用的最常見不良反應為肺炎（3%）和急性腎損傷（2%）。與 KEYTRUDA 相關的最常見不良反應（≥20%）包括噁心（56%）、疲勞（56%）、便秘（35%）、腹瀉（31%）、食慾減退（28%）、皮疹（25%）、嘔吐（24%）、咳嗽（21%）、呼吸困難（21%）和發熱（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，當 KEYTRUDA 與卡鉑和紫杉醇或紫杉醇蛋白結合物聯合用於轉移性鱗狀非小細胞肺癌時，101 名患者中有 15% 因不良反應停用 KEYTRUDA。至少 2% 的患者報告的最常見嚴重不良反應為發熱性中性粒細胞減少症、肺炎和尿路感染。KEYNOTE-407 中觀察到的與 KEYTRUDA 相關的不良反應與 KEYNOTE-189 中觀察到的相似，唯一的例外是 KEYTRUDA 和化療組的脱髮發生率（47% 對 36%）和周圍神經病（31% 對 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 因不良反應在 636 名晚期非小細胞肺癌患者中停用的比例為 19%；最常見的不良反應為肺炎（3%）、死因不明（1.6%）和肺炎（1.4%）。至少 2% 的患者報告的最常見嚴重不良反應為肺炎（7%）、肺炎（3.9%）、肺栓塞（2.4%）和胸腔積液（2.2%）。最常見的不良反應（≥20%）為疲勞（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 單藥治療在 682 名轉移性非小細胞肺癌患者中因不良反應停用的比例為 8%；最常見的不良反應為肺炎（1.8%）。最常見的不良反應（≥20%）為食慾減退（25%）、疲勞（25%）、呼吸困難（23%）和噁心（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 與鉑類化療聯合治療的可切除非小細胞肺癌患者的不良反應通常與其他臨牀試驗中接受 KEYTRUDA 與化療聯合治療的患者相似。

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 與化療或放化療聯合治療的患者中，最常見的不良反應（≥20%）包括疲勞/虛弱、噁心、便秘、腹瀉、食慾減退、皮疹、嘔吐、咳嗽、呼吸困難、發熱、脱髮、周圍神經病、粘膜炎、口腔炎、頭痛、體重減輕、腹痛、關節痛、肌肉痛、失眠、掌蹠紅斑、尿路感染、甲狀腺功能減退、放射性皮膚損傷、吞嚥困難、口乾和肌肉骨骼疼痛。

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 的輔助治療階段，當 KEYTRUDA 與鉑類化療聯合作為新輔助治療時，396 名患者中有 34% 出現嚴重不良反應。最常見的（≥2%）嚴重不良反應為肺炎（4.8%）、靜脈血栓栓塞（3.3%）和貧血（2%）。1.3% 的患者出現致命性不良反應，包括死因不明（0.8%）、膿毒症（0.3%）和免疫介導的肺病（0.3%）。因不良反應導致任何研究藥物永久停用的患者佔接受 KEYTRUDA 與鉑類化療聯合治療的患者的 18%；導致任何研究藥物永久停用的最常見不良反應（≥1%）為急性腎損傷（1.8%）、間質性肺病（1.8%）、貧血（1.5%）、中性粒細胞減少症（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%).

在接受新輔助治療的 KEYTRUDA 治療患者中，396 名患者中有 6% 因不良反應未能接受手術。導致 KEYTRUDA 組手術取消的最常見（≥1%）不良反應為間質性肺病（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 的輔助治療階段，當 KEYTRUDA 作為單藥進行輔助治療時，290 名患者中有 14% 出現嚴重不良反應。最常見的嚴重不良反應為肺炎（3.4%）。發生了一例致命性不良反應，即肺出血。因不良反應導致 KEYTRUDA 永久停用的患者佔接受 KEYTRUDA 單藥輔助治療的患者的 12%；導致 KEYTRUDA 永久停用的最常見不良反應（≥1%）為腹瀉（1.7%）、間質性肺病（1.4%）、天冬氨酸氨基轉移酶升高（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 中觀察到的不良反應通常與其他接受 KEYTRUDA 單藥治療的非小細胞肺癌患者相似，唯一的例外是甲狀腺功能減退（22%）、甲狀腺功能亢進（11%）和肺炎（7%）。發生了兩例致命性不良反應，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 中觀察到的不良反應通常與其他接受 KEYTRUDA 與培美曲塞和鉑類化療聯合治療的患者相似。

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 的患者中最常見的不良反應（≥20%）包括口腔炎（48%）、放射性皮膚損傷（40%）、體重減輕（36%）、疲勞（33%）、吞嚥困難（29%）、便秘（27%）、甲狀腺功能減退（26%）、噁心（24%）、皮疹（22%）、口乾（22%）、腹瀉（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 的新輔助階段，361 名接受至少一次單藥 KEYTRUDA 治療的患者中，有 11% 經歷了嚴重不良反應。發生在超過一名患者的嚴重不良反應包括肺炎（1.4%）、腫瘤出血（0.8%）、吞嚥困難（0.6%）、免疫介導的肝炎（0.6%）、蜂窩組織炎（0.6%）和呼吸困難（0.6%）。致命性不良反應發生在 1.1% 的患者中，包括呼吸衰竭、梭狀芽孢桿菌感染、膿毒性休克和心肌梗死（各一名患者）。因不良反應而永久停用 KEYTRUDA 的患者佔接受 KEYTRUDA 作為新輔助治療的患者的 2.8%。導致超過一名患者永久停用新輔助 KEYTRUDA 的最常見不良反應是關節痛（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 作為新輔助治療的患者中，有 11% 未接受手術。KEYTRUDA 組的手術取消原因包括疾病進展 4%、患者決定 3%、不良反應 1.4%、醫生決定 1.1%、腫瘤不可切除 0.6%、失訪 0.3% 以及使用非研究抗癌治療 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 治療並在新輔助階段後接受手術的患者中，有 1.2% 因不良反應經歷了手術延遲（定義為在新輔助 KEYTRUDA 開始後≥9 周進行的研究內手術），2.8% 因不良反應未接受輔助治療。

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 的輔助階段，255 名接受至少一次 KEYTRUDA 治療的患者中，有 38% 經歷了嚴重不良反應。報告在≥1% 的 KEYTRUDA 治療患者中最常見的嚴重不良反應包括肺炎（2.7%）、發熱（2.4%）、口腔炎（2.4%）、急性腎損傷（2.0%）、肺炎（1.6%）、COVID-19（1.2%）、未另行説明的死亡（1.2%）、腹瀉（1.2%）、吞嚥困難（1.2%）、胃造口管部位併發症（1.2%）和免疫介導的肝炎（1.2%）。致命性不良反應發生在 5% 的患者中，包括未另行説明的死亡（1.2%）、急性腎衰竭（0.4%）、高鈣血癥（0.4%）、肺出血（0.4%）、吞嚥困難/營養不良（0.4%）、腸繫膜血栓（0.4%）、膿毒症（0.4%）、肺炎（0.4%）、COVID-19（0.4%）、呼吸衰竭（0.4%）、心血管疾病（0.4%）和胃腸道出血（0.4%）。因不良反應而永久停用輔助 KEYTRUDA 的患者佔 17%。導致永久停用輔助 KEYTRUDA 的最常見（≥1%）不良反應包括肺炎、結腸炎、免疫介導的肝炎和未另行説明的死亡。

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 單藥治療；導致永久停用的最常見不良反應是膿毒症（1.7%）和肺炎（1.3%）。最常見的不良反應（≥20%）是疲勞（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，當 KEYTRUDA 與鉑類（順鉑或卡鉑）和氟尿嘧啶化療聯合使用時，276 名 HNSCC 患者中有 16% 因不良反應而停用 KEYTRUDA。導致永久停用 KEYTRUDA 的最常見不良反應是肺炎（2.5%）、肺炎（1.8%）和膿毒性休克（1.4%）。最常見的不良反應（≥20%）是噁心（51%）、疲勞（49%）、便秘（37%）、嘔吐（32%）、粘膜炎（31%）、腹瀉（29%）、食慾減退（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% 因不良反應而停用 KEYTRUDA。45% 的患者經歷了嚴重不良反應。至少 2% 的患者中最常見的嚴重不良反應包括肺炎、呼吸困難、意識混亂、嘔吐、胸腔積液和呼吸衰竭。最常見的不良反應（≥20%）是疲勞、食慾減退和呼吸困難。HNSCC 患者的發生的不良反應通常與接受 KEYTRUDA 單藥治療的黑色素瘤或非小細胞肺癌患者相似，唯一的例外是面部水腫和新發或加重的甲狀腺功能減退症的發生率增加。

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% 因不良反應而停用 KEYTRUDA。接受 KEYTRUDA 的患者中有 30% 經歷了嚴重不良反應；≥1% 的不良反應包括肺炎、肺炎、發熱、心肌炎、急性腎損傷、發熱性中性粒細胞減少症和膿毒症。有三名患者因非疾病進展原因死亡：2 名因異體造血幹細胞移植後併發症，1 名因未知原因。最常見的不良反應（≥20%）是上呼吸道感染（41%）、肌肉骨骼疼痛（32%）、腹瀉（22%）以及發熱、疲勞、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% 因不良反應而停用 KEYTRUDA。16% 的患者經歷了嚴重不良反應；≥1% 的不良反應包括肺炎、肺炎、發熱、呼吸困難、GVHD 和帶狀皰疹。有兩名患者因非疾病進展原因死亡：1 名因後續異體造血幹細胞移植後的 GVHD，1 名因膿毒性休克。最常見的不良反應（≥20%）是疲勞（26%）、發熱（24%）、咳嗽（24%）、肌肉骨骼疼痛（21%）、腹瀉（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% 因不良反應而停用 KEYTRUDA。26% 的患者經歷了嚴重不良反應，包括心律失常（4%）、心包壓塞（2%）、心肌梗死（2%）、心包積液（2%）和心包炎（2%）。六名（11%）患者在治療開始後 30 天內死亡。最常見的不良反應（≥20%）是肌肉骨骼疼痛（30%）、上呼吸道感染和發熱（各 28%）、咳嗽（26%）、疲勞（23%）和呼吸困難（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，當 KEYTRUDA 與 enfortumab vedotin 聯合用於局部晚期或轉移性尿路上皮癌患者（n=440）時，發生致命不良反應的比例為 3.9%，包括急性呼吸衰竭（0.7%）、肺炎（0.5%）和肺炎/間質性肺病（0.2%）。接受 KEYTRUDA 與 enfortumab vedotin 聯合治療的患者中，有 50% 出現嚴重不良反應；其中≥2% 的嚴重不良反應包括皮疹（6%）、急性腎損傷（5%）、肺炎/間質性肺病（4.5%）、尿路感染（3.6%）、腹瀉（3.2%）、肺炎（2.3%）、發熱（2%）和高血糖（2%）。由於不良反應，27% 的患者永久停用 KEYTRUDA。導致 KEYTRUDA 永久停用的最常見不良反應（≥2%）為肺炎/間質性肺病（4.8%）和皮疹（3.4%）。在接受 KEYTRUDA 與 enfortumab vedotin 聯合治療的患者中，發生的最常見不良反應（≥20%）為皮疹（68%）、周圍神經病（67%）、疲勞（51%）、瘙癢（41%）、腹瀉（38%）、脱髮（35%）、體重減輕（33%）、食慾減退（33%）、噁心（26%）、便秘（26%）、乾眼（24%）、味覺障礙（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，由於不良反應，370 名局部晚期或轉移性尿路上皮癌患者中有 11% 停用 KEYTRUDA。42% 的患者出現嚴重不良反應；其中≥2% 的包括尿路感染、血尿、急性腎損傷、肺炎和尿源性敗血症。最常見的不良反應（≥20%）為疲勞（38%）、肌肉骨骼疼痛（24%）、食慾減退（22%）、便秘（21%）、皮疹（21%）和腹瀉（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，由於不良反應，266 名局部晚期或轉移性尿路上皮癌患者中有 8% 停用 KEYTRUDA。導致 KEYTRUDA 永久停用的最常見不良反應為肺炎（1.9%）。39% 的 KEYTRUDA 治療患者出現嚴重不良反應；其中≥2% 的包括尿路感染、肺炎、貧血和肺炎。接受 KEYTRUDA 治療的患者中，最常見的不良反應（≥20%）為疲勞（38%）、肌肉骨骼疼痛（32%）、瘙癢（23%）、食慾減退（21%）、噁心（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 與 enfortumab vedotin 聯合治療的 MIBC 患者（n=167）中，發生的最常見不良反應（≥20%）為皮疹（54%）、瘙癢（47%）、疲勞（47%）、周圍神經病（39%）、脱髮（35%）、味覺障礙（35%）、腹瀉（34%）、便秘（28%）、食慾減退（28%）、噁心（26%）、尿路感染（24%）、乾眼（21%）和體重減輕（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 的輔助治療階段，27% 的患者（n=167）出現嚴重不良反應；最常見的（≥2%）為尿路感染（3.6%）和血尿（2.4%）。致命不良反應發生在 1.2% 的患者中，包括重症肌無力和毒性表皮壞死鬆解症（各 0.6%）。在輔助治療開始前的手術後階段，2.7% 的患者報告了額外的致命不良反應，包括膿毒症和腸梗阻（各 1.4%）。由於不良反應，15% 的患者永久停用 KEYTRUDA；最常見的（>1%）為皮疹（2.4%，包括廣泛性剝脱性皮炎）、丙氨酸氨基轉移酶升高、天冬氨酸氨基轉移酶升高、腹瀉、味覺障礙和毒性表皮壞死鬆解症（各 1.2%）。在接受 KEYTRUDA 與 enfortumab vedotin 聯合治療的 167 名患者中，有 7 名（4.2%）因不良反應未能接受手術。導致手術取消的不良反應包括急性心肌梗死、膽管癌、結腸癌、呼吸窘迫、尿路感染，以及因重症肌無力和毒性表皮壞死鬆解症導致的兩例死亡（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 與 enfortumab vedotin 聯合治療並進行根治性膀胱切除術的 146 名患者中，有 6 名（4.1%）因不良反應經歷手術延遲（定義為最後一次輔助治療到手術的時間超過 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 的輔助治療階段，43% 的患者（n=100）出現嚴重不良反應；最常見的（≥2%）為尿路感染（8%）；急性腎損傷和腎盂腎炎（各 5%）；尿源性敗血症（4%）；以及低鉀血癥、腸梗阻和膿毒症（各 2%）。7% 的患者發生致命不良反應，包括尿源性敗血症、顱內出血、死亡、心肌梗死、多臟器功能障礙綜合徵和假單胞菌肺炎（各 1%）。由於不良反應，28% 的患者永久停用 KEYTRUDA；最常見的（>1%）為腹瀉（5%）、周圍神經病、急性腎損傷和肺炎（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，由於不良反應，148 名高風險 NMIBC 患者中有 11% 停用 KEYTRUDA。導致 KEYTRUDA 永久停用的最常見不良反應為肺炎（1.4%）。28% 的患者出現嚴重不良反應；其中≥2% 的包括肺炎（3%）、心臟缺血（2%）、結腸炎（2%）、肺栓塞（2%）、膿毒症（2%）和尿路感染（2%）。最常見的不良反應（≥20%）為疲勞（29%）、腹瀉（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 單藥治療的 MSI-H 或 dMMR CRC 患者中，發生的不良反應與接受 KEYTRUDA 單藥治療的黑色素瘤或非小細胞肺癌患者相似。

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，發生在 MSI-H 或 dMMR 癌症患者中的不良反應與接受 KEYTRUDA 單藥治療的其他實體瘤患者相似。

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 與曲妥珠單抗和 CAPOX（卡培他濱加奧沙利鉑）或 FP（5-FU 加順鉑）聯合治療的 3 名患者發生了致命的不良反應，其中 2 名患者出現肺炎，1 名患者出現肝炎。在 350 名局部晚期不可切除或轉移性 HER2 陽性胃癌或 GEJ 腺癌患者中，因不良反應停用 KEYTRUDA 的比例為 13%。導致 KEYTRUDA 永久停用的≥1% 患者的不良反應包括肺炎（2.0%）和肺炎（1.1%）。在 KEYTRUDA 組與安慰劑組相比，接受 KEYTRUDA 治療的患者在腹瀉（53% vs 47%）、皮疹（35% vs 28%）、甲狀腺功能減退（11% vs 5%）和肺炎（11% vs 5%）方面的發生率差異≥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，當 KEYTRUDA 與含氟嘧啶和鉑類化療聯合使用時，785 名患者中有 45% 發生了嚴重不良反應。發生率超過 2% 的嚴重不良反應包括肺炎（4.1%）、腹瀉（3.9%）、出血（3.9%）和嘔吐（2.4%）。在接受 KEYTRUDA 的患者中，8% 發生了致命的不良反應，包括感染（2.3%）和血栓栓塞（1.3%）。因不良反應永久停用 KEYTRUDA 的患者比例為 15%。導致 KEYTRUDA 永久停用的最常見不良反應（≥1%）為感染（1.8%）和腹瀉（1.0%）。在接受 KEYTRUDA 與化療聯合治療的患者中，最常見的不良反應（發生率≥20%）為周圍神經病（47%）、噁心（46%）、疲勞（40%）、腹瀉（36%）、嘔吐（34%）、食慾減退（29%）、腹痛（26%）、掌蹠紅斑綜合徵（25%）、便秘（22%）和體重減輕（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，當 KEYTRUDA 與順鉑和氟尿嘧啶聯合用於不適合手術切除或確切化療放療的轉移性或局部晚期食管癌或 GEJ（腫瘤中心距 GEJ 1 至 5 厘米）患者時，370 名患者中有 15% 因不良反應停用 KEYTRUDA。導致 KEYTRUDA 永久停用的最常見不良反應（≥1%）為肺炎（1.6%）、急性腎損傷（1.1%）和肺炎（1.1%）。與化療聯合使用 KEYTRUDA 的最常見不良反應（≥20%）為噁心（67%）、疲勞（57%）、食慾減退（44%）、便秘（40%）、腹瀉（36%）、嘔吐（34%）、口腔炎（27%）和體重減輕（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 單藥治療的食管癌患者的不良反應與接受 KEYTRUDA 單藥治療的黑色素瘤或非小細胞肺癌患者的不良反應相似。

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，當 KEYTRUDA 與 CRT（順鉑加外照射放療 [EBRT] 後接種內放射治療 [BT]）聯合用於 FIGO 2014 III-IVA 期宮頸癌患者時，294 名患者中有 1.4% 發生了致命的不良反應，包括 1 例（0.3%）的大腸穿孔、尿源性敗血症、膿毒症和陰道出血。34% 的患者發生了嚴重不良反應；其中≥1% 的包括尿路感染（3.1%）、尿源性敗血症（1.4%）和膿毒症（1%）。因不良反應停用 KEYTRUDA 的患者比例為 9%。導致 KEYTRUDA 永久停用的最常見不良反應（≥1%）為腹瀉（1%）。對於接受 KEYTRUDA 與 CRT 聯合治療的患者，最常見的不良反應（≥10%）為噁心（56%）、腹瀉（51%）、尿路感染（35%）、嘔吐（34%）、疲勞（28%）、甲狀腺功能減退（23%）、便秘（20%）、體重減輕（19%）、食慾減退（18%）、發熱（14%）、腹痛和甲狀腺功能亢進（各 13%）、排尿困難和皮疹（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，當 KEYTRUDA 與紫杉醇和順鉑或紫杉醇和卡鉑聯合使用，是否伴隨貝伐單抗（n=307），用於持續、復發或一線轉移性宮頸癌患者，無論腫瘤 PD-L1 表達如何，且未接受過化療（除非作為放射增敏劑同時使用），4.6% 的患者發生了致命的不良反應，包括 3 例出血、2 例膿毒症和未知原因的病例，以及 1 例急性心肌梗死、自身免疫性腦炎、心臟驟停、腦血管意外、股骨骨折伴圍手術期肺栓塞、腸穿孔和盆腔感染。接受 KEYTRUDA 與化療聯合治療的患者中，50% 發生了嚴重不良反應；其中≥3% 的包括髮熱性中性粒細胞減少症（6.8%）、尿路感染（5.2%）、貧血（4.6%）和急性腎損傷及膿毒症（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%).

因不良反應停用 KEYTRUDA 的患者比例為 15%。導致 KEYTRUDA 永久停用的最常見不良反應（≥1%）為結腸炎（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%).

對於接受 KEYTRUDA、化療和貝伐單抗治療的患者（n=196），最常見的不良反應（≥20%）為周圍神經病（62%）、脱髮（58%）、貧血（55%）、疲勞/虛弱（53%）、噁心和中性粒細胞減少（各 41%）、腹瀉（39%）、高血壓和血小板減少（各 35%）、便秘和關節痛（各 31%）、嘔吐（30%）、尿路感染（27%）、皮疹（26%）、白細胞減少（24%）、甲狀腺功能減退（22%）和食慾減退（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%).

對於接受 KEYTRUDA 與化療聯合治療（有或沒有貝伐單抗）的患者，最常見的不良反應（≥20%）為周圍神經病（58%）、脱髮（56%）、疲勞（47%）、噁心（40%）、腹瀉（36%）、便秘（28%）、關節痛（27%）、嘔吐（26%）、高血壓和尿路感染（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 因不良反應在 98 名接受過治療的複發性或轉移性宮頸癌患者中停用，比例為 8%。接受 KEYTRUDA 的患者中，39% 出現嚴重不良反應；最常見的不良反應包括貧血（7%）、瘻管、出血和感染（尿路感染除外，均為 4.1%）。最常見的不良反應（≥20%）為疲勞（43%）、肌肉骨骼疼痛（27%）、腹瀉（23%）、疼痛和腹痛（均為 22%）以及食慾減退（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 因不良反應在 299 名接受過治療的肝細胞癌患者中停用，比例為 13%。導致 KEYTRUDA 永久停用的最常見不良反應為腹水（2.3%）。接受 KEYTRUDA 的患者中，最常見的不良反應（≥10%）為發熱（18%）、皮疹（18%）、腹瀉（16%）、食慾減退（15%）、瘙癢（12%）、上呼吸道感染（11%）、咳嗽（11%）和甲狀腺功能減退（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，當 KEYTRUDA 與吉西他濱和順鉑聯合使用時，KEYTRUDA 因不良反應在 529 名局部晚期不可切除或轉移性膽道癌患者中停用，比例為 15%。導致 KEYTRUDA 永久停用的最常見不良反應（≥1%）為肺炎（1.3%）。導致 KEYTRUDA 中斷的不良反應發生在 55% 的患者中。導致 KEYTRUDA 中斷的最常見不良反應或實驗室異常（≥2%）為中性粒細胞減少（18%）、血小板減少（10%）、貧血（6%）、白細胞減少（4%）、發熱（3.8%）、疲勞（3.0%）、膽管炎（2.8%）、ALT 升高（2.6%）、AST 升高（2.5%）和膽道梗阻（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，發生在 MCC 患者（n=105）中的不良反應通常與接受 KEYTRUDA 單藥治療的黑色素瘤或非小細胞肺癌患者相似。

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，當 KEYTRUDA 與阿昔替尼聯合使用時，429 名患者中發生致命不良反應的比例為 3.3%。40% 的患者出現嚴重不良反應，最常見的（≥1%）為肝毒性（7%）、腹瀉（4.2%）、急性腎損傷（2.3%）、脱水（1%）和肺炎（1%）。因不良反應永久停用 KEYTRUDA 的患者佔 31%；KEYTRUDA 單獨（13%）、阿昔替尼單獨（13%）和聯合治療（8%）；最常見的為肝毒性（13%）、腹瀉/結腸炎（1.9%）、急性腎損傷（1.6%）和腦血管意外（1.2%）。最常見的不良反應（≥20%）為腹瀉（56%）、疲勞/虛弱（52%）、高血壓（48%）、肝毒性（39%）、甲狀腺功能減退（35%）、食慾減退（30%）、掌蹠紅斑（28%）、噁心（28%）、口腔炎/黏膜炎（27%）、發音障礙（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，當 KEYTRUDA 作為單藥用於腎細胞癌的輔助治療時，接受 KEYTRUDA 的患者中發生嚴重不良反應的比例為 20%；嚴重不良反應（≥1%）包括急性腎損傷、腎上腺功能不全、肺炎、結腸炎和糖尿病酮症酸中毒（各 1%）。發生致命不良反應的比例為 0.2%，包括 1 例肺炎。因不良反應停用 KEYTRUDA 的患者佔 488 名患者的 21%；最常見的（≥1%）為 ALT 升高（1.6%）、結腸炎（1%）和腎上腺功能不全（1%）。最常見的不良反應（≥20%）為肌肉骨骼疼痛（41%）、疲勞（40%）、皮疹（30%）、腹瀉（27%）、瘙癢（23%）和甲狀腺功能減退（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，當 KEYTRUDA 與化療（紫杉醇和卡鉑）聯合用於 382 名晚期或複發性子宮內膜癌患者時，接受 KEYTRUDA 與化療聯合治療的患者中發生嚴重不良反應的比例為 35%，而接受安慰劑與化療聯合治療的患者中為 19%（n=377）。接受 KEYTRUDA 與化療聯合治療的患者中發生致命不良反應的比例為 1.6%，包括 COVID-19（0.5%）和心臟驟停（0.3%）。因不良反應停用 KEYTRUDA 的患者佔 14%。接受 KEYTRUDA 與化療聯合治療的患者中發生的不良反應通常與單獨使用 KEYTRUDA 或單獨使用化療的患者相似，唯一的例外是皮疹（33% 所有級別；3-4 級為 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 單藥治療的 MSI-H 或 dMMR 子宮內膜癌患者發生的不良反應與接受 KEYTRUDA 單藥治療的黑色素瘤或非小細胞肺癌患者相似。

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 單藥治療的 TMB-H 癌症患者發生的不良反應與接受 KEYTRUDA 單藥治療的其他實體瘤患者相似。

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 單藥治療的複發性或轉移性 cSCC 或局部晚期 cSCC 患者發生的不良反應與接受 KEYTRUDA 單藥治療的黑色素瘤或非小細胞肺癌患者相似。

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，當 KEYTRUDA 與新輔助化療（卡鉑和紫杉醇，隨後為多柔比星或表柔比星和環磷酰胺）聯合使用，並在手術後繼續單藥 KEYTRUDA 的輔助治療（n=778）時，針對新診斷的、未接受過治療的高風險早期三陰性乳腺癌患者，發生致命不良反應的比例為 0.9%，包括與多臟器功能障礙綜合徵和心肌梗死相關的腎上腺危機、自身免疫性腦炎、肝炎、肺炎、肺炎、肺栓塞和膿毒症各 1 例。接受 KEYTRUDA 治療的患者中，44% 發生嚴重不良反應；其中≥2% 的反應包括髮熱性中性粒細胞減少症（15%）、發熱（3.7%）、貧血（2.6%）和中性粒細胞減少症（2.2%）。由於不良反應，20% 的患者停止使用 KEYTRUDA。導致永久停藥的最常見反應（≥1%）為 ALT 升高（2.7%）、AST 升高（1.5%）和皮疹（1%）。接受 KEYTRUDA 與化療聯合治療後再單獨使用 KEYTRUDA 的患者中，最常見的不良反應（≥20%）為疲勞（70%）、噁心（67%）、脱髮（61%）、皮疹（52%）、便秘（42%）、腹瀉和周圍神經病（各 41%）、口腔炎（34%）、嘔吐（31%）、頭痛（30%）、關節痛（29%）、發熱（28%）、咳嗽（26%）、腹痛（24%）、食慾減退（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，當 KEYTRUDA 與化療（紫杉醇、紫杉醇蛋白結合或吉西他濱和卡鉑）聯合使用於未曾接受過化療的局部復發不可切除或轉移性三陰性乳腺癌患者（n=596）時，發生致命不良反應的比例為 2.5%，包括心肺驟停（0.7%）和膿毒性休克（0.3%）。接受 KEYTRUDA 與化療聯合治療的患者中，30% 發生嚴重不良反應；其中≥2% 的嚴重反應包括肺炎（2.9%）、貧血（2.2%）和血小板減少症（2%）。由於不良反應，11% 的患者停止使用 KEYTRUDA。導致永久停藥的最常見反應（≥1%）為 ALT 升高（2.2%）、AST 升高（1.5%）和肺炎（1.2%）。接受 KEYTRUDA 與化療聯合治療的患者中，最常見的不良反應（≥20%）為疲勞（48%）、噁心（44%）、脱髮（34%）、腹瀉和便秘（各 28%）、嘔吐和皮疹（各 26%）、咳嗽（23%）、食慾減退（21%）和頭痛（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，當 KEYTRUDA 與紫杉醇聯合使用（有或沒有貝伐單抗）時，54% 的患者發生了嚴重不良反應。≥2% 的患者中發生的嚴重不良反應包括肺炎（4.3%）、尿路感染（3.9%）、腎上腺功能不全（3%）、低鈉血癥（3%）、COVID-19、白細胞減少、肺栓塞（各 2.6%）、腹痛、貧血、結腸炎、腹瀉、發熱性中性粒細胞減少症、發熱和嘔吐（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 與紫杉醇聯合治療（有或沒有貝伐單抗）的患者中，發生致命不良反應的比例為 3.9%，包括協助自殺（0.9%）、死亡、腸穿孔、膿毒症、COVID-19、心肺驟停、結腸炎和栓塞性中風（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).

由於不良反應，16% 的患者永久停用 KEYTRUDA。導致 KEYTRUDA 永久停藥的最常見不良反應（≥1%）為結腸炎和丙氨酸氨基轉移酶升高（各 1.3%）。導致 KEYTRUDA 中斷的反應發生在 44% 的患者中。導致 KEYTRUDA 中斷的最常見不良反應（≥2%）為尿路感染（3.9%）、腎上腺功能不全、發熱、肺炎、上呼吸道感染（各 2.6%）、中性粒細胞減少症、腹瀉和 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 與紫杉醇聯合治療（有或沒有貝伐單抗）的患者中，最常見的不良反應（≥20%）為腹瀉（45%）、疲勞（43%）、噁心（41%）、脱髮、周圍神經病（各 38%）、鼻出血（31%）、尿路感染（27%）、便秘（25%）、腹痛、食慾減退、嘔吐（各 24%）、甲狀腺功能減退（21%）、咳嗽、高血壓和皮疹（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.

對於接受 KEYTRUDA 與紫杉醇和貝伐單抗聯合治療的患者（N=169），還報告了白細胞減少（27%）、口腔炎（22%）和發熱（21%）作為不良反應。

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.

由於母乳餵養兒童可能出現嚴重不良反應，建議女性在治療期間及最後一次給藥後 4 個月內不要哺乳。

Pediatric Use

兒童使用

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 名兒童患者（65 名 6 個月至 12 歲以下的兒童和 108 名 12 至 17 歲的兒童）接受了每 3 周 2 mg/kg 的 KEYTRUDA 治療。中位暴露時間為 2.1 個月（範圍：1 天至 25 個月）。

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%).

與成人相比，兒童患者中發生≥10% 更高比例的不良反應包括髮熱（33%）、白細胞減少（30%）、嘔吐（29%）、中性粒細胞減少（28%）、頭痛（25%）、腹痛（23%）、血小板減少（22%）、3 級貧血（17%）、淋巴細胞減少（13%）和白細胞減少（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 與恩福妥單抗聯合治療的局部晚期或轉移性尿路上皮癌患者中，44%（n=247）為 65-74 歲，26%（n=144）為 75 歲或以上。65 歲及以上患者與年輕患者之間的療效沒有明顯差異。接受 KEYTRUDA 與恩福妥單抗聯合治療的 75 歲及以上患者發生致命不良反應的比例高於年輕患者。75 歲以下患者的致命不良反應發生率為 4%，而 75 歲及以上患者為 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 與 enfortumab vedotin 聯合治療的 MIBC 患者中，37%（n=61）年齡在 65-74 歲之間，46%（n=77）年齡在 75 歲或以上。75 歲及以上的患者在接受 KEYTRUDA 與 enfortumab vedotin 聯合治療時，出現致命不良反應的發生率高於年輕患者。75 歲以下患者的致命不良反應發生率為 4%，而 75 歲及以上患者的發生率為 12%。

Additional Selected KEYTRUDA Indications in the U.S.

美國 KEYTRUDA 的其他適應症

Melanoma

黑色素瘤

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

KEYTRUDA 適用於治療不可切除或轉移性黑色素瘤患者。

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 適用於在完全切除後對成人和兒童（12 歲及以上）IIB、IIC 或 III 期黑色素瘤患者進行輔助治療。

Malignant Pleural Mesothelioma

惡性胸膜間皮瘤

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 與 pemetrexed 和鉑類化療聯合使用，適用於不可切除的晚期或轉移性惡性胸膜間皮瘤（MPM）成人患者的一線治療。

Head and Neck Squamous Cell Cancer

頭頸部鱗狀細胞癌

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 適用於治療可切除的局部晚期頭頸部鱗狀細胞癌（HNSCC）成人患者，前提是其腫瘤表達 PD-L1 [綜合陽性評分（CPS）≥1]，根據 FDA 授權的檢測作為單藥新輔助治療，隨後作為輔助治療與放療（RT）聯合使用，可能包括或不包括順鉑，然後作為單藥治療。

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 與鉑類和氟尿嘧啶（FU）聯合使用，適用於轉移性或不可切除、複發性 HNSCC 患者的一線治療。

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 作為單藥，適用於轉移性或不可切除、複發性 HNSCC 患者的一線治療，前提是其腫瘤表達 PD-L1（CPS ≥1），根據 FDA 授權的檢測。

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 作為單藥，適用於在鉑類化療後病情進展的複發性或轉移性 HNSCC 患者的治療。

Classical Hodgkin Lymphoma

經典霍奇金淋巴瘤

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

KEYTRUDA 適用於治療復發或難治性經典霍奇金淋巴瘤（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 適用於治療複發性 cHL 或在兩條或更多治療方案後復發的兒童患者。

Primary Mediastinal Large B-Cell Lymphoma

原發性縱隔大 B 細胞淋巴瘤

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 適用於治療複發性原發性縱隔大 B 細胞淋巴瘤（PMBCL）的成人和兒童患者，或在兩條或更多治療方案後復發的患者。KEYTRUDA 不推薦用於需要緊急細胞減滅治療的 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 與 enfortumab vedotin 聯合使用，適用於局部晚期或轉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 作為單藥，適用於局部晚期或轉移性尿路上皮癌患者的治療：

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.

不適合任何鉑類化療，或
在鉑類化療期間或之後病情進展，或在新輔助或輔助鉑類化療後 12 個月內病情進展。

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 與 enfortumab vedotin 聯合使用，作為新輔助治療，隨後在膀胱切除術後繼續作為輔助治療，適用於不適合順鉑化療的肌肉浸潤性膀胱癌（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 作為單藥，適用於對巴氏桿菌卡介苗（BCG）無反應的高風險非肌肉浸潤性膀胱癌（NMIBC）患者的治療，這些患者有原位癌（CIS）伴或不伴乳頭狀腫瘤，且不適合或選擇不進行膀胱切除術。

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

微衞星不穩定性高或錯配修復缺陷癌症

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 適用於治療不可切除或轉移性微衞星不穩定性高（MSI-H）或錯配修復缺陷（dMMR）實體瘤的成人和兒童患者，前提是根據 FDA 授權的檢測，患者在先前治療後病情進展且沒有滿意的替代治療選擇。

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

微衞星不穩定性高或錯配修復缺陷結直腸癌

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 適用於治療不可切除或轉移性 MSI-H 或 dMMR 結直腸癌（CRC）患者，前提是根據 FDA 授權的檢測。

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 與曲妥珠單抗、氟嘧啶類和鉑類化療聯合使用，適用於局部晚期不可切除或轉移性 HER2 陽性胃癌或胃食管交界（GEJ）腺癌的成人患者，前提是其腫瘤表達 PD-L1（CPS ≥1），根據 FDA 授權的檢測。

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 與氟嘧啶類和鉑類化療聯合使用，適用於局部晚期不可切除或轉移性 HER2 陰性胃癌或胃食管交界（GEJ）腺癌的成人患者，前提是其腫瘤表達 PD-L1（CPS ≥1），根據 FDA 授權的檢測。

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 適用於治療局部晚期或轉移性食管或胃食管交界（GEJ）癌症（腫瘤中心距 GEJ 1 至 5 厘米）患者，這些患者不適合外科切除或確切的化學放療：

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.

與鉑類和氟嘧啶類化療聯合使用，適用於腫瘤表達 PD-L1（CPS ≥1）的患者，或
作為單藥，適用於在一條或多條系統治療後病情進展的腫瘤為鱗狀細胞組織學且表達 PD-L1（CPS ≥10）的患者，前提是根據 FDA 授權的檢測。

Cervical Cancer

宮頸癌

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 與化療放療（CRT）聯合使用，適用於治療局部晚期宮頸癌患者，該癌症涉及陰道下三分之一，伴或不伴有向盆腔側壁的擴展，或腎積水/非功能性腎臟，或擴散至鄰近盆腔器官（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 與化療聯合使用，伴或不伴貝伐單抗，適用於治療持續性、複發性或轉移性宮頸癌患者，其腫瘤表達 PD-L1（CPS ≥1），由 FDA 授權的檢測確定。

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 作為單一藥物，適用於治療在化療後病情進展的複發性或轉移性宮頸癌患者，其腫瘤表達 PD-L1（CPS ≥1），由 FDA 授權的檢測確定。

Hepatocellular Carcinoma

肝細胞癌

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 適用於治療因乙型肝炎引起的肝細胞癌（HCC）患者，這些患者已接受過除含 PD-1/PD-L1 方案以外的系統治療。

Biliary Tract Cancer

膽道癌

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 與吉西他濱和順鉑聯合使用，適用於治療局部晚期不可切除或轉移性膽道癌（BTC）患者。

Merkel Cell Carcinoma

梅克爾細胞癌

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

KEYTRUDA 適用於治療複發性局部晚期或轉移性梅克爾細胞癌（MCC）的成人和兒童患者。

Renal Cell Carcinoma

腎細胞癌

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

KEYTRUDA 與阿昔替尼聯合使用，適用於治療成人晚期腎細胞癌（RCC）的首選治療。

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 適用於腎細胞癌患者的輔助治療，這些患者在腎切除術後存在中高風險或高風險復發，或在腎切除術後及轉移病灶切除後。

Endometrial Carcinoma

子宮內膜癌

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 與卡鉑和紫杉醇聯合使用，隨後作為單一藥物繼續使用，適用於治療成人原發性晚期或複發性子宮內膜癌患者。

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 作為單一藥物，適用於治療 MSI-H 或 dMMR 的晚期子宮內膜癌成人患者，這些患者在任何環境下的先前系統治療後病情進展，且不適合進行治癒性手術或放療，由 FDA 授權的檢測確定。

Tumor Mutational Burden-High Cancer

腫瘤突變負荷高癌症

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 適用於治療不可切除或轉移性腫瘤突變負荷高（TMB-H）[≥10 突變/兆鹼基（mut/Mb）] 的成人和兒童患者，由 FDA 授權的檢測確定，這些患者在先前治療後病情進展，且沒有令人滿意的替代治療選擇。

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.

該適應症在腫瘤反應率和反應持續性基礎上獲得加速批准。該適應症的持續批准可能取決於在確認性試驗中驗證和描述臨牀益處。尚未確定 KEYTRUDA 在 TMB-H 中樞神經系統癌症兒童患者中的安全性和有效性。

Cutaneous Squamous Cell Carcinoma

皮膚鱗狀細胞癌

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 適用於治療複發性或轉移性皮膚鱗狀細胞癌（cSCC）或局部晚期 cSCC，這些癌症無法通過手術或放療治癒。

Triple-Negative Breast Cancer

三陰性乳腺癌

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 適用於治療高風險早期三陰性乳腺癌（TNBC）患者，聯合化療作為新輔助治療，手術後繼續作為單一藥物進行輔助治療。

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 與化療聯合使用，適用於治療局部復發不可切除或轉移性 TNBC 患者，其腫瘤表達 PD-L1（CPS ≥10），由 FDA 授權的檢測確定。

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 與紫杉醇聯合使用，伴或不伴貝伐單抗，適用於治療鉑耐藥的上皮卵巢癌、輸卵管癌或原發性腹膜癌的成人患者，其腫瘤表達 PD-L1（CPS ≥1），由 FDA 授權的檢測確定，且這些患者已接受過一或兩種先前的系統治療方案。

About Gilead and Kite Oncology

關於吉利德和 Kite 腫瘤學

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 腫瘤學致力於改變癌症的治療方式。我們正在通過下一代療法、組合和技術進行創新，以改善癌症患者的治療結果。我們有意識地構建我們的腫瘤學產品組合和管道，以解決護理中的最大差距。從抗體藥物偶聯技術和小分子到基於細胞治療的方法，我們正在為癌症患者創造新的可能性。

About Gilead Sciences

關於吉利德科學

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.

吉利德科學公司是一家生物製藥公司，三十多年來致力於醫學突破，目標是為所有人創造一個更健康的世界。該公司致力於推進創新藥物，以預防和治療危及生命的疾病，包括 HIV、病毒性肝炎、COVID-19、癌症和炎症。2025 年，吉利德宣佈計劃投資 320 億美元，以進一步增強其在美國的影響力，推動下一個發現、創造就業和公共衞生準備的時代，同時繼續在全球範圍內投資，以確保各地患者受益於其科學創新。吉利德在全球 35 個國家運營，總部位於加利福尼亞州福斯特城。

Forward Looking Statements

前瞻性聲明

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.

本新聞稿包含 1995 年《私人證券訴訟改革法案》所定義的前瞻性聲明，這些聲明受到風險、不確定性和其他因素的影響，包括吉利德在當前預期時間內啓動、推進或完成臨牀試驗的能力，或根本無法完成，以及正在進行或額外臨牀試驗（包括涉及 sacituzumab govitecan-hziy 的試驗，如 EVOKE-03）可能產生的不利結果；與監管申請及相關提交和批准時間表的相關不確定性，包括對 sacituzumab govitecan-hziy 的額外待審和潛在申請，以及任何監管批准（如果獲得）可能受到重大使用限制或被相關監管機構撤回或採取其他不利行動的風險；吉利德可能做出戰略決定，停止對當前正在評估的適應症（包括用於治療轉移性非小細胞肺癌的 sacituzumab govitecan-hziy）開發項目的開發，因此這些項目可能永遠無法商業化；以及任何上述內容所依據的假設。這些風險、不確定性和其他因素在吉利德截至2026年3月31日的季度報告（10-Q 表格）中詳細描述，已提交給美國證券交易委員會。這些風險、不確定性和其他因素可能導致實際結果與前瞻性聲明中提到的結果存在重大差異。所有非歷史事實的聲明均可視為前瞻性聲明。讀者應注意，任何此類前瞻性聲明並不保證未來的表現，並涉及風險和不確定性，且應謹慎對待這些前瞻性聲明。所有前瞻性聲明均基於吉利德當前可獲得的信息，吉利德不承擔任何更新此類前瞻性聲明的義務，並對此不表示任何意圖。

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

Trodelvy、Gilead 及 Gilead 標誌是 Gilead Sciences, Inc.或其相關公司的商標。

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

Trodelvy 的美國處方信息，包括 盒裝警告，可在 www.gilead.com 獲取。

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).

有關吉利德的更多信息，請訪問公司網站 www.gilead.com，關注吉利德的 X/Twitter（@Gilead Sciences）和 LinkedIn（@Gilead-Sciences）。

About Merck

關於默克

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（在美國和加拿大以外稱為 MSD），我們團結一致，圍繞我們的使命：我們利用尖端科學的力量，拯救和改善全球人們的生活。130 多年來，我們通過開發重要的藥物和疫苗為人類帶來了希望。我們渴望成為全球首屈一指的研究密集型生物製藥公司——今天，我們處於研究的前沿，提供創新的健康解決方案，推動人類和動物疾病的預防和治療。我們培養多元和包容的全球勞動力，每天負責任地運營，以實現所有人和社區的安全、可持續和健康的未來。有關更多信息，請訪問 www.merck.com，並在 X（前身為 Twitter）、Facebook、Instagram、YouTube 和 LinkedIn 上與我們聯繫。

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

默克公司（Merck & Co., Inc.）的前瞻性聲明，位於美國新澤西州拉威

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.

本新聞稿來自默克公司（Merck & Co., Inc.），位於美國新澤西州拉威（“公司”），包括根據 1995 年《美國私人證券訴訟改革法案》的安全港條款定義的 “前瞻性聲明”。這些聲明基於公司管理層當前的信念和期望，並受到重大風險和不確定性的影響。對於管道候選者，無法保證這些候選者將獲得必要的監管批准或證明其商業成功。如果基礎假設不準確或風險或不確定性實現，實際結果可能與前瞻性聲明中所述的結果存在重大差異。

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.

風險和不確定性包括但不限於一般行業狀況和競爭；一般經濟因素，包括利率和匯率波動；製藥行業監管和美國及國際醫療立法的影響；全球醫療成本控制的趨勢；技術進步、競爭對手獲得的新產品和專利；新產品開發中固有的挑戰，包括獲得監管批准；公司準確預測未來市場條件的能力；製造困難或延誤；國際經濟的財務不穩定和主權風險；依賴於公司對創新產品的專利和其他保護的有效性；以及面臨訴訟（包括專利訴訟）和/或監管行動的風險。

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).

公司沒有義務公開更新任何前瞻性聲明，無論是由於新信息、未來事件還是其他原因。可能導致結果與前瞻性聲明中描述的結果存在重大差異的其他因素可以在公司截至2025年12月31日的年度報告（10-K 表格）和公司向證券交易委員會（SEC）提交的其他文件中找到，這些文件可在 SEC 的互聯網網站（www.sec.gov）上獲取。

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 .

請參閲 KEYTRUDA（pembrolizumab）的處方信息，網址為 http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf 以及 KEYTRUDA 的藥物指南，網址為 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:

吉利德聯繫方式：

Priscilla White, Media

Priscilla White, 媒體

Public_affairs@gilead.com

Jacquie Ross, Investor

Jacquie Ross, 投資者

investor_relations@gilead.com

Merck Media Contact:

默克媒體聯繫人：

Julie Cunningham

julie.cunningham@merck.com

Merck Investor Relations Contact:

默克投資者關係聯繫人：

Steven Graziano

(732) 594-1583

Source: Merck & Co., Inc.

來源：默克公司。

默克和吉利德科學更新了 3 期 KEYNOTE-D46/EVOKE-03 研究的進展 | MRK 股票新聞