First-line pembrolizumab plus chemotherapy for advanced/metastatic esophageal cancer: 1-year extended follow-up in the Japanese subgroup of the phase 3 KEYNOTE-590 study

Ken Kato; Takashi Kojima; Hiroki Hara; Akihito Tsuji; Hisateru Yasui; Kei Muro; Taroh Satoh; Takashi Ogata; Ryu Ishihara; Masahiro Goto; Hideo Baba; Tomohiro Nishina; ShiRong Han; Keiichi Iwakami; Naoyoshi Yatsuzuka; Toshihiko Doi

doi:10.1007/s10388-024-01053-z

First-line pembrolizumab plus chemotherapy for advanced/metastatic esophageal cancer: 1-year extended follow-up in the Japanese subgroup of the phase 3 KEYNOTE-590 study

Esophagus. 2024 Apr 12. doi: 10.1007/s10388-024-01053-z. Online ahead of print.

Authors

Ken Kato¹, Takashi Kojima², Hiroki Hara³, Akihito Tsuji⁴, Hisateru Yasui⁵, Kei Muro⁶, Taroh Satoh⁷, Takashi Ogata⁸, Ryu Ishihara⁹, Masahiro Goto¹⁰, Hideo Baba¹¹, Tomohiro Nishina¹², ShiRong Han¹³, Keiichi Iwakami¹³, Naoyoshi Yatsuzuka¹³, Toshihiko Doi²

Affiliations

¹ Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. kenkato@ncc.go.jp.
² Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan.
³ Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan.
⁴ Department of Medical Oncology, Kagawa University Hospital, Miki, Kagawa, Japan.
⁵ Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan.
⁶ Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.
⁷ Center for Cancer Genomics and Precision Medicine, Osaka University Hospital, Osaka, Japan.
⁸ Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan.
⁹ Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan.
¹⁰ Cancer Chemotherapy Center, Osaka Medical and Pharmaceutical University Hospital, Osaka, Japan.
¹¹ Department of Gastroenterological Surgery, Kumamoto University Hospital, Kumamoto, Japan.
¹² Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Ehime, Japan.
¹³ Department of Medical Oncology, MSD K.K., Tokyo, Japan.

PMID: 38607538
DOI: 10.1007/s10388-024-01053-z

Abstract

Background: First-line pembrolizumab plus chemotherapy (pembrolizumab-chemotherapy) demonstrated improved efficacy and a manageable safety profile versus placebo plus chemotherapy (placebo-chemotherapy) in the subgroup analysis of Japanese patients with advanced/metastatic esophageal cancer in KEYNOTE-590 at a median follow-up of 24.4 months. Longer-term data from the Japanese subgroup analysis of KEYNOTE-590 are reported.

Methods: Patients were randomly assigned 1:1 to pembrolizumab 200 mg or placebo every 3 weeks for ≤ 35 cycles plus chemotherapy (cisplatin 80 mg/m² and 5-fluorouracil 800 mg/m²/day). Endpoints included overall survival (OS) and progression-free survival (PFS; investigator-assessed per RECIST v1.1; dual primary) and safety (secondary). Early tumor shrinkage (ETS) and depth of response (DpR) were assessed post hoc.

Results: Overall, 141 patients were enrolled in Japan. As of July 9, 2021, median follow-up was 36.6 months (range, 29.8-45.7). Pembrolizumab-chemotherapy showed a trend toward favorable OS (hazard ratio [HR], 0.70; 95% confidence interval [CI] 0.47-1.03) and PFS (0.57; 0.39-0.83) versus placebo-chemotherapy. In the pembrolizumab-chemotherapy group, patients with ETS ≥ 20% (55/74; 74.3%) versus < 20% (19/74; 25.7%) had favorable OS (HR, 0.23; 95% CI 0.12-0.42) and PFS (0.24; 0.13-0.43). Patients with DpR ≥ 60% (31/74; 41.9%) versus < 60% (43/74; 58.1%) had favorable OS (HR, 0.37; 95% CI 0.20-0.68) and PFS (0.24; 0.13-0.43). Grade 3-5 treatment-related adverse events occurred in 55/74 patients (74.3%) with pembrolizumab-chemotherapy and 41/67 patients (61.2%) with placebo-chemotherapy.

Conclusions: With longer-term follow-up of Japanese patients with advanced/metastatic esophageal cancer, efficacy continued to favor pembrolizumab-chemotherapy compared with placebo-chemotherapy, with no new safety signals observed.

Clinical trial registration: ClinicalTrials.gov, NCT03189719.

Keywords: Esophageal squamous cell carcinoma; Immune checkpoint inhibitors; Immunotherapy; Pembrolizumab; Programmed cell death ligand 1.

Associated data

ClinicalTrials.gov/NCT03189719