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

• Published in: Cancer Vol. 128; no. 5; pp. 995 - 1003
• Main Authors: Chung, Hyun Cheol, Kang, Yoon‐Koo, Chen, Zhendong, Bai, Yuxian, Wan Ishak, Wan Zamaniah, Shim, Byoung Yong, Park, Young Lee, Koo, Dong‐Hoe, Lu, Jianwei, Xu, Jianming, Chon, Hong Jae, Bai, Li‐Yuan, Zeng, Shan, Yuan, Ying, Chen, Yen‐Yang, Gu, Kangsheng, Zhong, Wen Yan, Kuang, Shu, Shih, Chie‐Schin, Qin, Shu‐Kui
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.03.2022; John Wiley and Sons Inc
• Subjects: Antibodies, Monoclonal, Humanized - adverse effects; Asia; Cancer; chemotherapy; China; Confidence intervals; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - pathology; Esophagogastric Junction - pathology; Gastric cancer; gastroesophageal junction cancer; Health care facilities; Humans; Immunotherapy; Monoclonal antibodies; Oncology; Original; Paclitaxel; Paclitaxel - adverse effects; Patients; PD-L1 protein; Pembrolizumab; programmed death 1; Solid tumors; Stomach Neoplasms - drug therapy; Stomach Neoplasms - pathology; Survival; Targeted cancer therapy; Tumors; China; pembrolizumab; gastroesophageal junction cancer; gastric cancer; Asia; chemotherapy; programmed death 1
• ISSN: 0008-543X; 1097-0142; 1097-0142
• DOI: 10.1002/cncr.34019

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. In this small sample of Asian patients with advanced PD‐L1–positive (combined positive score [CPS] ≥1) gastric/gastroesophageal junction (GEJ) cancer enrolled in the randomized, open‐label, phase 3 KEYNOTE‐063 study, definitive conclusions on clinical outcomes are limited; however, second‐line pembrolizumab monotherapy seems to be well tolerated in this patient population. These findings are consistent with those of the larger global KEYNOTE‐061 study in patients with CPS ≥1 gastric/GEJ cancer.