Pembrolizumab plus chemotherapy for advanced HER2-negative gastric or gastroesophageal junction cancer: KEYNOTE-859 Q-TWiST analysis.

IF 2.3 4区医学 Q3 IMMUNOLOGY

Immunotherapy Pub Date : 2026-02-01 Epub Date: 2026-04-11 DOI:10.1080/1750743X.2026.2647579

Lucjan Wyrwicz, Vasiliki Kalampoki, Adriana Valderrama, Kate Young

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引用次数: 0

Abstract

Aims: In KEYNOTE-859, pembrolizumab plus chemotherapy significantly improved overall survival (OS) versus placebo plus chemotherapy for participants with untreated locally advanced or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma, with manageable safety. This post hoc analysis assessed Quality-adjusted Time Without Symptoms of disease progression or Toxicity of treatment (Q-TWiST).

Participants and methods: Survival time was grouped into three health states: TOX (time with any grade ≥3 adverse event [AE] before disease progression), TWiST (time before PD or death without grade ≥3 AEs), and REL (time from PD to death). Q-TWiST was the sum of restricted mean survival time (RMST) in each state, weighted by utilities estimated using the EQ-5D-5L questionnaire. Relative gains in Q-TWiST ≥15% were considered "clearly clinically important."

Results: RMST was longer in TOX (2.30 months [95% CI, 1.28 to 3.44]) and TWiST (1.90 months [95% CI, -0.02 to 3.79]) and shorter in REL (-0.28 months [95% CI, -2.43 to 2.01]) with pembrolizumab plus chemotherapy versus chemotherapy at month 56, for a relative Q-TWiST gain of 20.90% (US algorithm) or 18.38% (standardized algorithm).

Conclusions: A clearly clinically important Q-TWiST gain was observed with pembrolizumab plus chemotherapy versus chemotherapy in all participants.

Clinical trials registration: www.ClinicalTrials.gov identifier is NCT03675737.

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派姆单抗联合化疗治疗晚期her2阴性胃癌或胃食管结癌：KEYNOTE-859 Q-TWiST分析

目的：在KEYNOTE-859中，对于未经治疗的局部晚期或转移性her2阴性胃或胃食管连接处腺癌患者，派姆单抗加化疗与安慰剂加化疗相比，显着提高了总生存期（OS），安全性可控。该事后分析评估了无疾病进展症状或治疗毒性的质量调整时间（Q-TWiST）。参与者和方法：将生存时间分为三种健康状态：TOX（疾病进展前发生≥3级不良事件[AE]的时间）、TWiST（发生PD或死亡前无≥3级AE的时间）和REL（从PD到死亡的时间）。Q-TWiST是每个州的限制平均生存时间（RMST）的总和，通过EQ-5D-5L问卷估计的效用加权。Q-TWiST的相对增益≥15%被认为“明显具有临床重要性”。结果：在第56个月时，派姆单抗联合化疗与化疗相比，TOX组（2.30个月[95% CI， 1.28至3.44]）和TWiST组（1.90个月[95% CI， -0.02至3.79]）的RMST更长，REL组（-0.28个月[95% CI， -2.43至2.01]）的相对Q-TWiST增益为20.90% （US算法）或18.38%（标准化算法）。结论：在所有参与者中，派姆单抗联合化疗与化疗相比，观察到明显具有重要临床意义的Q-TWiST增益。临床试验注册：www.ClinicalTrials.gov标识符：NCT03675737。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Immunotherapy 医学-免疫学

CiteScore

5.00

自引率

3.60%

发文量

113

审稿时长

6-12 weeks

期刊介绍： Many aspects of the immune system and mechanisms of immunomodulatory therapies remain to be elucidated in order to exploit fully the emerging opportunities. Those involved in the research and clinical applications of immunotherapy are challenged by the huge and intricate volumes of knowledge arising from this fast-evolving field. The journal Immunotherapy offers the scientific community an interdisciplinary forum, providing them with information on the most recent advances of various aspects of immunotherapies, in a concise format to aid navigation of this complex field. Immunotherapy delivers essential information in concise, at-a-glance article formats. Key advances in the field are reported and analyzed by international experts, providing an authoritative but accessible forum for this vitally important area of research. Unsolicited article proposals are welcomed and authors are required to comply fully with the journal''s Disclosure & Conflict of Interest Policy as well as major publishing guidelines, including ICMJE and GPP3.