Phase IIb study of pembrolizumab combined with S-1 + oxaliplatin or S-1 + cisplatin as first-line chemotherapy for gastric cancer.

Abstract

The KEYNOTE-659 study evaluated the efficacy and safety of first-line pembrolizumab plus S-1 and oxaliplatin (SOX) (cohort 1) or S-1 and cisplatin (SP) (cohort 2) for advanced gastric/gastroesophageal junction (G/GEJ) cancer in Japan. Herein, we update the results of cohort 1 and describe the results of cohort 2. This open-label phase IIb study enrolled patients with advanced programmed death-ligand 1 (PD-L1)-positive (combined positive score ≥ 1) human epidermal growth factor receptor 2 (HER2)-negative G/GEJ adenocarcinoma. The primary end-point was the objective response rate (ORR). Other end-points were duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. One hundred patients were enrolled. In cohorts 1 and 2, median follow-up time was 16.9 and 17.1 months; ORR (central review), 72.2% and 80.4%; DOR, 10.6 and 9.5 months; DCR (central review), 96.3% and 97.8%; median PFS (central review), 9.4 and 8.3 months; and median OS, 16.9 and 17.1 months, respectively. Treatment-related adverse events (TRAEs) occurred in all patients, including peripheral sensory neuropathy (94.4%, cohort 1), decreased neutrophil count (82.6%, cohort 2), nausea (59.3% and 60.9% in cohorts 1 and 2), and decreased appetite (61.1% and 60.9% in cohorts 1 and 2). Grade 3 or higher TRAEs were reported by 59.3% (cohort 1) and 78.3% (cohort 2), including decreased platelet count (14.8%, cohort 1) and decreased neutrophil count (52.2%, cohort 2). Pembrolizumab in combination with SOX or SP showed favorable efficacy and safety in patients with PD-L1-positive, HER2-negative G/GEJ adenocarcinoma.

• Authors: Kensei Yamaguchi, Keiko Minashi, Daisuke Sakai, Tomohiro Nishina, Yasushi Omuro, Masahiro Tsuda, Shiroh Iwagami, Hisato Kawakami, Taito Esaki, Naotoshi Sugimoto, Takashi Oshima, Ken Kato, Kenji Amagai, Hisashi Hosaka, Keigo Komine, Hisateru Yasui, Yuji Negoro, Kenji Ishido, Takahiro Tsushima, Shirong Han, Shinichi Shiratori, Tomoko Takami, Kohei Shitara
• Journal: Cancer science (Cancer Sci) Vol. 113 Issue 8 Pg. 2814-2827 (Aug 2022) ISSN: 1349-7006 [Electronic] England
• PMID: 35701865 (Publication Type: Clinical Trial, Phase II, Journal Article)
• Copyright: © 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• Antibodies, Monoclonal, Humanized
• B7-H1 Antigen
• Oxaliplatin
• pembrolizumab
• Cisplatin

Topics

• Adenocarcinoma (drug therapy, pathology)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• B7-H1 Antigen (metabolism)
• Cisplatin (therapeutic use)
• Esophageal Neoplasms
• Humans
• Oxaliplatin (therapeutic use)
• Stomach Neoplasms (drug therapy, pathology)