First-line pembrolizumab + chemotherapy in Japanese patients with advanced/metastatic esophageal cancer from KEYNOTE-590

BACKGROUND: The phase 3 KEYNOTE-590 (NCT03189719) study showed first-line pembrolizumab plus chemotherapy significantly prolonged overall survival and progression-free survival versus placebo plus chemotherapy in patients with advanced unresectable or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or advanced/metastatic Siewert type I adenocarcinoma of the esophagogastric junction. We describe a subgroup analysis of Japanese patients from KEYNOTE-590. METHODS: Eligible patients were randomly assigned 1:1 to pembrolizumab 200 mg intravenously every 3 weeks or placebo plus chemotherapy (cisplatin 80 mg/m(2) and 5-fluorouracil 800 mg/m(2)/day). Efficacy was evaluated in all Japanese patients and those with esophageal squamous cell carcinoma and programmed death ligand 1 combined positive score ≥ 10. Dual primary endpoints were overall survival and progression-free survival per RECIST v1.1 by investigator. Secondary endpoints included objective response rate per RECIST v1.1 by investigator and safety and tolerability. RESULTS: At data cutoff (July 2, 2020), 141 Japanese patients were randomly assigned (pembrolizumab plus chemotherapy, 74; placebo plus chemotherapy, 67). In all Japanese patients, median overall survival was 17.6 months with pembrolizumab plus chemotherapy versus 11.7 months with chemotherapy (hazard ratio, 0.71; 95% confidence interval, 0.47–1.09), median progression-free survival was 6.3 versus 6.0 months (hazard ratio, 0.58; 95% confidence interval, 0.40–0.84), and objective response rate was 56.8% versus 38.8%. Grade 3–5 treatment-related adverse events were 74.3% and 61.2%. CONCLUSION: First-line pembrolizumab plus chemotherapy demonstrated improvement in overall survival and progression-free survival compared with placebo plus chemotherapy in Japanese patients with advanced/metastatic esophageal cancer; safety was comparable between treatment groups. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov, NCT03189719. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10388-022-00920-x.