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Clinical Trial
. 2022 Aug;113(8):2814-2827.
doi: 10.1111/cas.15462. Epub 2022 Jul 1.

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

Kensei Yamaguchi  1 , Keiko Minashi  2 , Daisuke Sakai  3 , Tomohiro Nishina  4 , Yasushi Omuro  5 , Masahiro Tsuda  6 , Shiroh Iwagami  7 , Hisato Kawakami  8 , Taito Esaki  9 , Naotoshi Sugimoto  10 , Takashi Oshima  11 , Ken Kato  12 , Kenji Amagai  13 , Hisashi Hosaka  14 , Keigo Komine  15 , Hisateru Yasui  16 , Yuji Negoro  17 , Kenji Ishido  18 , Takahiro Tsushima  19 , Shirong Han  20 , Shinichi Shiratori  21 , Tomoko Takami  21 , Kohei Shitara  22   23
Affiliations
Clinical Trial

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

Kensei Yamaguchi et al. Cancer Sci. 2022 Aug.

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.

Keywords: S-1; cisplatin; gastric cancer; oxaliplatin; pembrolizumab.

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Figures

FIGURE 1
FIGURE 1
Overall tumor response in Japanese patients with gastric cancer treated with (A) first‐line pembrolizumab with S‐1 + oxaliplatin (cohort 1) or (B) first‐line pembrolizumab with S‐1 + cisplatin (cohort 2), assessed by central review according to RECIST version 1.1. Best change from baseline in the sum of the longest target lesion diameter per patient by programmed cell death‐ligand 1 expression. CPS, combined positive score
FIGURE 2
FIGURE 2
Kaplan–Meier estimates of progression‐free survival in Japanese patients with gastric cancer treated with (A) first‐line pembrolizumab with S‐1 + oxaliplatin (cohort 1) or (B) first‐line pembrolizumab with S‐1 + cisplatin (cohort 2), assessed by central review
FIGURE 3
FIGURE 3
Kaplan–Meier estimates of overall survival in Japanese patients with gastric cancer treated with (A) first‐line pembrolizumab with S‐1 + oxaliplatin (cohort 1) or (B) first‐line pembrolizumab with S‐1 + cisplatin (cohort 2)
FIGURE 4
FIGURE 4
Kaplan–Meier estimates of progression‐free survival in Japanese patients with gastric cancer treated with (A) first‐line pembrolizumab with S‐1 + oxaliplatin (cohort 1) or (B) first‐line pembrolizumab with S‐1 + cisplatin (cohort 2) according to combined positive score (CPS), assessed by central review
FIGURE 5
FIGURE 5
Kaplan–Meier estimates of overall survival in Japanese patients with gastric cancer treated with (A) first‐line pembrolizumab with S‐1 + oxaliplatin (cohort 1) or (B) first‐line pembrolizumab with S‐1 + cisplatin (cohort 2) according to combined positive score (CPS)
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