Discussion
tumor, gastric/GEJ cancer, toxicity, MSI-H, gastric cancer disease, gastric cancer
CPS, TUMOR, GASTRIC CANCER
These subgroup analyses of Japanese patients with gastric/GEJ cancer demonstrated that pembrolizumab monotherapy, given as first-, second-, or third-line and later therapy, demonstrated a trend toward improvement in clinical outcomes, although the results were not statistically significant compared with placebo. Data from KEYNOTE-061 and KEYNOTE-062 also demonstrated numeric improvement in median OS with pembrolizumab monotherapy compared with chemotherapy in patients with PD-L1 CPS ≥ 1. Analyses from KEYNOTE-062 also suggested improvements in median OS and PFS with pembrolizumab in patients with CPS ≥ 10; however, these differences were not statistically tested. In all three studies, pembrolizumab was generally well tolerated, produced no unexpected toxicity, and had a better safety profile than chemotherapy.Findings from these Japanese subgroup analyses are comparable with outcomes observed in the intention-to-treat (ITT) populations of each respective study. In KEYNOTE-059, OS and PFS medians were similar between the Japanese subgroup and the ITT population [Similar outcomes were also observed in the Japanese subgroup and the ITT population in KEYNOTE-061 patients with CPS ≥ 1 for OS and PFS medians, and no significant differences were observed in either population between pembrolizumab and chemotherapy [In KEYNOTE-062, median OS in the Japanese subgroup with CPS ≥ 1 was higher in the pembrolizumab and chemotherapy groups (20 and 18 months, respectively) than in the ITT population (11 and 11 months), but no significant between-treatment differences were observed in either population; median PFS in the pembrolizumab group of the Japanese subgroup was also higher (6 months) than it was in the ITT population (2 months) [When multiple factors influence prognosis, a combination of these factors can affect the OS HR between two treatment groups. To confirm whether the HRs were robust in our study, we performed multivariate analysis of OS after adjusting for selected baseline characteristics. We found that OS HRs ranged from 0.5 to 0.7 for an imbalanced combination of factors, supporting the robustness of our results. Furthermore, in KEYNOTE-062, 134 of 254 pembrolizumab-treated patients (53%) and 132 of 244 chemotherapy-treated patients (54%) received ≥ 1 subsequent anticancer therapy in the total population [PD-L1 expression can be used in clinical practice to help select patients for treatment with immunotherapy in tumor types with high PD-L1 expression. In GC, use of CPS is a robust and reproducible predictive marker to identify patients likely to respond to pembrolizumab [Pembrolizumab monotherapy was generally well tolerated in the Japanese subgroups of KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062, which were comparable with the ITT population [The results of the current report for the subgroup of patients enrolled at Japanese sites in the KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 studies demonstrated the efficacy and safety of pembrolizumab in previously untreated and treated Japanese patients and showed general consistency with data from globally conducted studies. These results not only build on existing data from global studies but add to the body of evidence evaluating pembrolizumab in various patient populations in the gastric cancer treatment setting. Analyses that differ in geographic region of enrollment enable regulatory agencies and health care providers to make decisions based on the benefit-to-risk ratio of pembrolizumab across various patient populations and ultimately facilitate swift access to needed treatments by patients, which is especially important in the gastric cancer disease setting.Limitations of the current retrospective analysis include small sample sizes for the Japanese subgroups in each study (≤ 100 patients) as well subgroups for CPS ≥ 10 and MSI-H status; thus, results should be interpreted with caution. Additionally, the current analysis included the KEYNOTE-061 study, which did not meet its primary end points of OS and PFS in patients with a PD-L1 CPS ≥ 1.