Disparity in survival benefits of pembrolizumab between Asian and non‐Asian patients with advanced cancers: A systematic review and meta‐regression analysis

Abstract

Abstract Background Immune checkpoint inhibitors have revolutionized the treatment of malignancies. However, disproportionate enrollment among races and ethnicities places the generalizability of global trial results in doubt. Methods In this systematic review, phase 3 randomized controlled trials investigating pembrolizumab in advanced cancers and providing subgroup analyses of Asian and non‐Asian participants were included. The primary and secondary effect measures were the mean differences (MDs) in the natural logarithms of the hazard ratios (HRs) for overall survival (OS) and progression‐free survival (PFS) between these two subgroups, respectively. We used random‐effects meta‐analysis to calculate the pooled ratios of HRs (i.e., exp(MD)) and implemented a meta‐regression analysis to identify significant covariates. Results A total of 17 and 11 trials were included in the meta‐analyses of OS and PFS, respectively. These trials included 2732 (25.49%) Asian and 7000 (65.32%) non‐Asian participants in the OS analysis and 1438 (22.5%) Asian and 4129 (64.61%) non‐Asian participants in the PFS analysis. The pooled ratio of HRs for OS was 0.87 (95% CI: 0.76–0.99; p = 0.0391), favoring Asian participants, but no significant difference was found in PFS (pooled ratio of HRs: 0.93; 95% CI: 0.82–1.07; p = 0.2391). Both linear meta‐regression analyses revealed an open‐label design as a crucial covariate, which indicated more benefits for non‐Asian participants. Conclusions Compared with non‐Asian patients, Asian patients with advanced cancers may derive superior OS benefits from pembrolizumab. Although the results warrant further exploration, this meta‐analysis provides insight into clinical research design.

Keywords

• advanced cancers
• Asian
• meta‐analysis
• overall survival
• pembrolizumab