Pembrolizumab in microsatellite-instability-high and mismatch-repair-deficient advanced solid tumors: updated results of the KEYNOTE-158 trial

IF 28.5 1区医学 Q1 ONCOLOGY Nature cancer Pub Date : 2025-02-20 DOI:10.1038/s43018-024-00894-y

Aurelien Marabelle, David M. O’Malley, Andrew E. Hendifar, Paolo A. Ascierto, Daniel Motola-Kuba, Nicolas Penel, Philippe A. Cassier, Giovanni Bariani, Ana De Jesus-Acosta, Toshihiko Doi, Federico Longo, Wilson H. Miller Jr, Do-Youn Oh, Maya Gottfried, Lili Yao, Fan Jin, Alexander Gozman, Michele Maio

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Abstract

The phase 2 trial KEYNOTE-158 ( NCT02628067 ) evaluated pembrolizumab in microsatellite-instability-high and mismatch-repair-deficient (MSI-H/dMMR) noncolorectal tumors. With 373 participants (95% with baseline MSI/dMMR documentation) and 4.5 years of follow-up, the primary endpoint of overall response rate was 33.8%. Secondary endpoints of duration of response, overall survival and progression-free survival were 63.2, 19.8 and 4.0 months, respectively. Grade ≥3 treatment-related adverse events occurred in 50 (13%) participants. These results further support pembrolizumab use in MSI-H/dMMR tumors. Marabelle et al. present updated data from the KEYNOTE-158 trial after ~4.5 years of follow-up, reporting an overall response rate of 34% and a median overall survival of 19.8 months in participants with MSI-H/MMR advanced noncolorectal solid tumors.

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Pembrolizumab治疗微卫星不稳定性高和错配修复缺陷晚期实体瘤：KEYNOTE-158试验的最新结果

ii期试验KEYNOTE-158 （NCT02628067）评估了派姆单抗在微卫星不稳定性高和错配修复缺陷（MSI-H/dMMR）非结直肠肿瘤中的治疗效果。373名参与者（95%具有基线MSI/dMMR文件）和4.5年的随访，总缓解率的主要终点为33.8%。次要终点反应持续时间、总生存期和无进展生存期分别为63.2个月、19.8个月和4.0个月。50名（13%）参与者发生≥3级治疗相关不良事件。这些结果进一步支持派姆单抗在MSI-H/dMMR肿瘤中的应用。

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来源期刊

Nature cancer Medicine-Oncology

CiteScore

31.10

自引率

1.80%

发文量

129

期刊介绍： Cancer is a devastating disease responsible for millions of deaths worldwide. However, many of these deaths could be prevented with improved prevention and treatment strategies. To achieve this, it is crucial to focus on accurate diagnosis, effective treatment methods, and understanding the socioeconomic factors that influence cancer rates. Nature Cancer aims to serve as a unique platform for sharing the latest advancements in cancer research across various scientific fields, encompassing life sciences, physical sciences, applied sciences, and social sciences. The journal is particularly interested in fundamental research that enhances our understanding of tumor development and progression, as well as research that translates this knowledge into clinical applications through innovative diagnostic and therapeutic approaches. Additionally, Nature Cancer welcomes clinical studies that inform cancer diagnosis, treatment, and prevention, along with contributions exploring the societal impact of cancer on a global scale. In addition to publishing original research, Nature Cancer will feature Comments, Reviews, News & Views, Features, and Correspondence that hold significant value for the diverse field of cancer research.