Pembrolizumab vs paclitaxel as second-line treatment for Asian patients with PD-L1–positive advanced gastric or gastroesophageal cancer (GC) in the phase III KEYNOTE-063 trial.
e16586 Background: Approximately 75% of GC cases occur in Asian persons. Pembrolizumab has shown antitumor activity in global studies of GC. KEYNOTE-063 (NCT03019588) is a randomized, open-label, phase 3 trial in Asian patients with advanced PD-L1–positive (combined positive score [CPS] ≥1) GC that progressed after platinum + fluoropyrimidine chemotherapy. After the KEYNOTE-063 study began, results of the global KEYNOTE-061 study (NCT02370498) showed that pembrolizumab did not prolong overall survival (OS) vs paclitaxel in patients previously treated for advanced GC (median OS, 9.1 months vs 8.3 months; hazard ratio [HR], 0.82; 95% CI, 0.66-1.03; 1-sided P= 0.0421 [significance threshold for OS was 1-sided P= 0.0135]). Methods: Eligible patients were randomly assigned in a 1:1 ratio to receive pembrolizumab 200 mg Q3W for up to 35 cycles (~2 years) or standard-dose paclitaxel. The primary efficacy end points were OS and progression-free survival (PFS). Planned enrollment was ~360 patients. Results: Because pembrolizumab did not significantly prolong OS in KEYNOTE-061, enrollment in KEYNOTE-063 was discontinued after 94 patients were enrolled (47 patients in each treatment group). In these Asian patients, median OS was 8.4 months in the pembrolizumab group and 7.7 months in the paclitaxel group; median PFS was 1.9 months and 4.0 months, respectively (Table). Objective response rate (ORR) and median duration of response (DOR) are shown in the Table. Drug-related adverse events (AEs) occurred in 59.6% of patients receiving pembrolizumab and in 95.5% of patients receiving paclitaxel (Table). Conclusions: In this small sample of Asian patients with PD-L1–positive advanced GC, definitive conclusions are limited; however, second-line pembrolizumab monotherapy seems to be well tolerated in this patient population. Because this study was terminated early, there was insufficient power for comparisons between groups; therefore, these data should be viewed with caution. Clinical trial information: NCT03019588 . [Table: see text]