Geographic heterogeneity in the outcomes of patients receiving immune checkpoint inhibitors for advanced solid tumors: a meta-analysis.

Abstract

BackgroundLittle is known about the effect of geographic location on efficacy of immune checkpoint inhibitors (ICI). We performed a systematic review and meta-analysis to assess the heterogeneity of ICI efficacy between different geographic locations.MethodsWe searched PubMed, EMBASE, and the Cochrane Library through October 2019 for phase III randomized controlled trials (RCT) that provided sufficient data for hazard ratio (HR) and 95% confidence interval (CI) of overall survival (OS) or progression-free survival (PFS) according to designated geographic region. We calculated pooled HRs and 95% CIs for North American, European and Asian cancer patients, and assessed data heterogeneity using subgroup and sensitivity analysis. The INPLASY registration number was INPLASY202050062.ResultsOf 10151 publications identified in our research, 17 RCTs including 7462 patients met our selection criteria. The pooled HRs for OS of North American, European and Asian patients were 0.67 (95% CI: 0.57 to 0.78), 0.72 (95% CI: 0.64 to 0.81), and 0.74 (95% CI: 0.66 to 0.84) respectively; the pooled HRs for PFS of North American, European and Asian patients were 0.58 (95% CI: 0.49 to 0.69), 0.61 (95% CI: 0.41 to 0.90), and 0.87 (95% CI: 0.38 to 1.99) respectively. Both anti-PD-1 inhibitors and anti-PD-L1 inhibitors showed clinical benefit in North American and European arms while anti-PD-L1 inhibitors failed to show benefit in Asian arms.ConclusionsOur meta-analysis indicates that the magnitude of benefit from ICI varies in North America, Europe, and Asia. Asian patients experience inferior outcomes compared to Western patients. Notably, anti-PD-L1 therapies do not result in survival improvements in Asian patients.