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

• Published in: Cancer science 2022-08, Vol.113 (8), p.2814-2827
• Main Authors: Yamaguchi, Kensei, Minashi, Keiko, Sakai, Daisuke, Nishina, Tomohiro, Omuro, Yasushi, Tsuda, Masahiro, Iwagami, Shiroh, Kawakami, Hisato, Esaki, Taito, Sugimoto, Naotoshi, Oshima, Takashi, Kato, Ken, Amagai, Kenji, Hosaka, Hisashi, Komine, Keigo, Yasui, Hisateru, Negoro, Yuji, Ishido, Kenji, Tsushima, Takahiro, Han, Shirong, Shiratori, Shinichi, Takami, Tomoko, Shitara, Kohei
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Apoptosis; Appetite loss; Cancer therapies; Chemotherapy; Cisplatin; Cysts; Disease control; Enrollments; Epidermal growth factor; ErbB-2 protein; Gastric cancer; Leukocytes (neutrophilic); Nausea; Original; ORIGINAL ARTICLES; Oxaliplatin; Patients; PD-L1 protein; Pembrolizumab; Peripheral neuropathy; Population; Potassium; Safety; Steroids; S‐1
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.15462

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. The KEYNOTE‐659 study was a multicenter, open‐label phase IIb study that evaluated the efficacy and safety of first‐line pembrolizumab with S‐1 + oxaliplatin (cohort 1) or S‐1 + cisplatin (cohort 2) for advanced gastric/gastroesophageal junction cancer in Japan. In cohorts 1 and 2, the median follow‐up times were 16.9 and 17.1 months, respectively; the objective response rates (primary endpoint) were 72.2% and 80.4%, respectively; and treatment‐related adverse events 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). First‐line pembrolizumab with S‐1 + oxaliplatin or S‐1 + cisplatin showed favorable efficacy and manageable safety in PD‐L1‐positive, H