Pembrolizumab vs chemotherapy as 2L therapy for advanced esophageal cancer: Japanese Subgroup Analysis in KEYNOTE-181

Abstract

Abstract Background Safe and effective treatment of advanced esophageal cancer is an area of unmet need. KEYNOTE-181 is a global, randomized, open-label, phase 3 study of pembrolizumab (PBR) vs chemotherapy (SoC) as second-line therapy for pts with advanced or metastatic esophageal cancer. Methods Eligible pts were aged ≥18 y, had confirmed, advanced adenocarcinoma (AC) or squamous cell carcinoma of the esophagus (ESCC), or HER2-negative Siewert type 1 AC of the gastroesophageal junction, documented progression on 1 prior-line therapy, measurable disease per RECIST v1.1, ECOG PS 0 or 1, and provision of a tumor sample for biomarker analysis. Pts were randomized 1:1 to PBR 200 mg Q3W for 2 years or investigator’s choice of paclitaxel 80-100 mg/m 2 on days 1, 8, and 15 of every 28-day cycle, docetaxel 75 mg/m 2 Q3W, or irinotecan 180 mg/m 2 Q2W. Stratification was by histology and geographic region. Primary endpoints were OS in the ITT, ESCC, and PD-L1 combined positive score (CPS) ≥10 populations. Secondary endpoints were PFS and ORR, by RECIST v1.1, and safety. Results Of the 152 Japanese pts enrolled, 133 (88%) were male, 94 (62%) had ECOG PS 0, 149 (98%) had ESCC, and 79 (52%) had PD-L1 CPS ≥10. Pts were randomized to PBR (77 pts) or SoC (75 pts), and median follow-up durations were 11.5 mo (range, 1.0-29.2) and 8.2 mo (range, 0.8-32.2), respectively. Median OS was improved with PBR vs SoC in pts with PD-L1 CPS ≥10 (12.5 vs 8.4 mo; HR 0.70; 95%CI 0.43-1.13; P = 0.0682), in pts with ESCC (11.9 vs 8.2 mo; HR 0.68; 95%CI 0.48-0.97; P = 0.0156) and in the ITT population (11.5 vs 8.2 mo; HR 0.68; 95%CI 0.48-0.96; P = 0.0147). These 3 primary OS data in Japanese were consistent to entire global populations, respectively. Fewer pts had any-grade (74% vs 96%) or grade 3-5 (17% vs 50%) drug-related AEs with PBR vs SoC. Conclusion PBR improved OS compared with SoC as second-line therapy for advanced esophageal cancer in Japanese patients, with a more favorable safety profile than SoC.