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

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%) drugrelated 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.