{"title":"一线派姆单抗加化疗治疗日本胃或胃食管交界腺癌患者：KEYNOTE-859 iii期研究的亚组分析","authors":"Hisateru Yasui, Masaki Aizawa, Kensei Yamaguchi, Akihito Kawazoe, Hiroki Hara, Masahiro Tsuda, Hirokazu Shoji, Naotoshi Sugimoto, Nobuhiro Shibata, Kenji Amagai, Yasuhiro Choda, Shiro Iwagami, Taito Esaki, Shigenori Kadowaki, Shinichi Shiratori, Shirong Han, Sonal Bordia, Kohei Shitara","doi":"10.1007/s10147-025-02847-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>In the global phase 3 KEYNOTE-859 study (NCT03675737), first-line pembrolizumab plus chemotherapy significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) versus placebo plus chemotherapy in participants with advanced human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma. This post hoc analysis of KEYNOTE-859 evaluated outcomes in participants enrolled in Japan.</p><p><strong>Methods: </strong>Participants with untreated locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma were randomly assigned to receive pembrolizumab 200 mg or placebo intravenously every 3 weeks for ≤ 35 cycles plus investigator's choice of chemotherapy. The primary end point was OS. Secondary end points were ORR, DOR, and PFS per RECIST v1.1, by blinded independent central review, and safety. Data cutoff was October 3, 2022.</p><p><strong>Results: </strong>Overall, 101 participants were enrolled in Japan (n = 48 pembrolizumab plus chemotherapy [pembrolizumab group]; n = 53 placebo plus chemotherapy [placebo group]). Median follow-up was 28.9 months (range, 22.0-42.0). Median OS was 16.8 months with pembrolizumab versus 13.3 months with placebo (hazard ratio [HR], 0.71; 95% CI, 0.44-1.13). Grade 3 or 4 treatment-related adverse events occurred in 41.7% of participants given pembrolizumab and 39.6% of participants given placebo; none were grade 5.</p><p><strong>Conclusions: </strong>Consistent with the global KEYNOTE-859 results, OS was better with pembrolizumab plus chemotherapy, with manageable safety, for participants enrolled in Japan. Results continue to support pembrolizumab plus chemotherapy as a new first-line treatment option for patients with advanced or metastatic HER2-negative gastric or GEJ adenocarcinoma.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT03675737.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":"2003-2011"},"PeriodicalIF":2.8000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"First-line pembrolizumab plus chemotherapy for participants in Japan with gastric or gastroesophageal junction adenocarcinoma: subgroup analysis of the phase 3 KEYNOTE-859 study.\",\"authors\":\"Hisateru Yasui, Masaki Aizawa, Kensei Yamaguchi, Akihito Kawazoe, Hiroki Hara, Masahiro Tsuda, Hirokazu Shoji, Naotoshi Sugimoto, Nobuhiro Shibata, Kenji Amagai, Yasuhiro Choda, Shiro Iwagami, Taito Esaki, Shigenori Kadowaki, Shinichi Shiratori, Shirong Han, Sonal Bordia, Kohei Shitara\",\"doi\":\"10.1007/s10147-025-02847-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>In the global phase 3 KEYNOTE-859 study (NCT03675737), first-line pembrolizumab plus chemotherapy significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) versus placebo plus chemotherapy in participants with advanced human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma. This post hoc analysis of KEYNOTE-859 evaluated outcomes in participants enrolled in Japan.</p><p><strong>Methods: </strong>Participants with untreated locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma were randomly assigned to receive pembrolizumab 200 mg or placebo intravenously every 3 weeks for ≤ 35 cycles plus investigator's choice of chemotherapy. The primary end point was OS. Secondary end points were ORR, DOR, and PFS per RECIST v1.1, by blinded independent central review, and safety. Data cutoff was October 3, 2022.</p><p><strong>Results: </strong>Overall, 101 participants were enrolled in Japan (n = 48 pembrolizumab plus chemotherapy [pembrolizumab group]; n = 53 placebo plus chemotherapy [placebo group]). Median follow-up was 28.9 months (range, 22.0-42.0). Median OS was 16.8 months with pembrolizumab versus 13.3 months with placebo (hazard ratio [HR], 0.71; 95% CI, 0.44-1.13). Grade 3 or 4 treatment-related adverse events occurred in 41.7% of participants given pembrolizumab and 39.6% of participants given placebo; none were grade 5.</p><p><strong>Conclusions: </strong>Consistent with the global KEYNOTE-859 results, OS was better with pembrolizumab plus chemotherapy, with manageable safety, for participants enrolled in Japan. Results continue to support pembrolizumab plus chemotherapy as a new first-line treatment option for patients with advanced or metastatic HER2-negative gastric or GEJ adenocarcinoma.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT03675737.</p>\",\"PeriodicalId\":13869,\"journal\":{\"name\":\"International Journal of Clinical Oncology\",\"volume\":\" \",\"pages\":\"2003-2011\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Clinical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10147-025-02847-6\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/1 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Clinical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10147-025-02847-6","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/1 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
First-line pembrolizumab plus chemotherapy for participants in Japan with gastric or gastroesophageal junction adenocarcinoma: subgroup analysis of the phase 3 KEYNOTE-859 study.
Background: In the global phase 3 KEYNOTE-859 study (NCT03675737), first-line pembrolizumab plus chemotherapy significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) versus placebo plus chemotherapy in participants with advanced human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma. This post hoc analysis of KEYNOTE-859 evaluated outcomes in participants enrolled in Japan.
Methods: Participants with untreated locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma were randomly assigned to receive pembrolizumab 200 mg or placebo intravenously every 3 weeks for ≤ 35 cycles plus investigator's choice of chemotherapy. The primary end point was OS. Secondary end points were ORR, DOR, and PFS per RECIST v1.1, by blinded independent central review, and safety. Data cutoff was October 3, 2022.
Results: Overall, 101 participants were enrolled in Japan (n = 48 pembrolizumab plus chemotherapy [pembrolizumab group]; n = 53 placebo plus chemotherapy [placebo group]). Median follow-up was 28.9 months (range, 22.0-42.0). Median OS was 16.8 months with pembrolizumab versus 13.3 months with placebo (hazard ratio [HR], 0.71; 95% CI, 0.44-1.13). Grade 3 or 4 treatment-related adverse events occurred in 41.7% of participants given pembrolizumab and 39.6% of participants given placebo; none were grade 5.
Conclusions: Consistent with the global KEYNOTE-859 results, OS was better with pembrolizumab plus chemotherapy, with manageable safety, for participants enrolled in Japan. Results continue to support pembrolizumab plus chemotherapy as a new first-line treatment option for patients with advanced or metastatic HER2-negative gastric or GEJ adenocarcinoma.
期刊介绍：
The International Journal of Clinical Oncology (IJCO) welcomes original research papers on all aspects of clinical oncology that report the results of novel and timely investigations. Reports on clinical trials are encouraged. Experimental studies will also be accepted if they have obvious relevance to clinical oncology. Membership in the Japan Society of Clinical Oncology is not a prerequisite for submission to the journal. Papers are received on the understanding that: their contents have not been published in whole or in part elsewhere; that they are subject to peer review by at least two referees and the Editors, and to editorial revision of the language and contents; and that the Editors are responsible for their acceptance, rejection, and order of publication.
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