Pembrolizumab versus paclitaxel for previously treated advanced gastric or gastroesophageal junction cancer (KEYNOTE-063): A randomized, open-label, phase 3 trial in Asian patients

Abstract

Background: KEYNOTE-063 (NCT03019588) investigated pembrolizumab versus paclitaxel as second-line therapy in Asian patients with advanced programmed death ligand 1 (PD-L1)-positive (combined positive score ≥1) gastric/gastroesophageal junction (GEJ) cancer.

Methods: This randomized, open-label, phase 3 study was conducted at 36 medical centers in China (mainland), Malaysia, South Korea, and Taiwan. Patients were randomly assigned 1:1 to 200 mg of pembrolizumab intravenously every 3 weeks for ≤2 years or 80 mg/m2 of paclitaxel intravenously every week. Primary end points were overall survival (OS) and progression-free survival (PFS). Secondary end points were objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 and safety.

Results: Between February 16, 2017, and March 12, 2018, 94 patients were randomly assigned (47 pembrolizumab/47 paclitaxel) after screening; enrollment was stopped on March 12, 2018, based on the results of the global KEYNOTE-061 study, and patients were followed until the last patient's last visit. Median OS was 8 months (95% confidence interval [CI], 4-10 months) with pembrolizumab versus 8 months (95% CI, 5-11 months) with paclitaxel (hazard ratio [HR], 0.99; 95% CI, 0.63-1.54). Median PFS was 2 months (95% CI, 1-3 months) with pembrolizumab versus 4 months (95% CI, 3-6 months) with paclitaxel (HR, 1.62; 95% CI, 1.04-2.52). ORR was 13% for pembrolizumab versus 19% for paclitaxel. Any-grade treatment-related adverse events occurred in 28 pembrolizumab-treated patients (60%) and 42 paclitaxel-treated patients (96%); grades 3 to 5 events occurred in 5 patients (11%) and 28 patients (64%), respectively.

Conclusions: Definitive conclusions about the efficacy of second-line pembrolizumab in Asian patients with advanced PD-L1-positive gastric/GEJ cancer are limited because of insufficient power, but pembrolizumab was well tolerated in this patient population. Efficacy followed a trend similar to that observed in the phase 3 KEYNOTE-061 trial.

Keywords: Asia; chemotherapy; gastric cancer; gastroesophageal junction cancer; pembrolizumab; programmed death 1.

Conflict of interest statement

Hyun Cheol Chung reports grants (for research to institution) from Amgen, Bristol‐Myers Squibb/Ono, Eli Lilly, GSK, Incyte, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey, Merck‐Serono, Taiho, and Zymework; honoraria from Eli Lilly and Merck‐Serono; and consultancy fees from Amgen, BeiGene, Bristol‐Myers Squibb, Celltrion, Eli Lilly, Gloria, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey, Merck‐Serono, Quintiles, Taiho, and Zymeworks. Yoon‐Koo Kang reports advisory fees from ALX Oncology, Amgen, Bristol‐Myers Squibb, Daehwa, Macrogenics, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey, Novartis, Surface Oncology, and Zymeworks. Wan Zamaniah Wan Ishak reports honoraria for lectures from Amgen Malaysia, DKSH Malaysia, Eisai Malaysia, Eli Lilly Malaysia, Ipsen Malaysia, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey, Merck Serono Malaysia, Pfizer Malaysia, and Roche Malaysia; travel grants from Amgen Malaysia, Celgene Malaysia, Eisai Malaysia, Eli Lilly Malaysia, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey, and Roche Malaysia; and is an advisory board member for Celgene Malaysia, Eli Lilly Malaysia, Eisai Malaysia, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey. Wen Yan Zhong is an employee of MSD China, Beijing, China. Shu Kuang is an employee of MSD China, Beijing, China. Chie‐Schin Shih is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey and a stockholder of Merck & Co., Inc., Kenilworth, New Jersey.

© 2021 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.

Figures

Figure 1

Patient disposition. aIntended enrollment for KEYNOTE‐063 was 360 but was halted at 94 because pembrolizumab did not significantly prolong overall survival over paclitaxel in the KEYNOTE‐061 study (NCT02370498). bThere was no maximum number of doses of paclitaxel. ITT indicates intention‐to‐treat.

Figure 2

Kaplan‐Meier estimates of overall survival.

Figure 3

Kaplan‐Meier estimates of progression‐free survival.

Figure 4

Kaplan‐Meier estimates of duration of response.