Effect of region on the Outcome of Patients Receiving PD-1/PD-L1 Inhibitors for Advanced Cancer

Abstract Background Regional differences were associated with cancer incidence and mortality. However, the correlation between regional differences and cancer immunotherapy efficacy was still not evaluated. In this study, we performed a meta-analysis to investigate whether regional differences play a role in efficacy of PD-1/L1 inhibitors in cancer patients. Methods A meticulous review of relevant randomized controlled trials that were sourced from the PubMed, Embase and MEDLINE databases. Overall survival (OS) and progression-free survival (PFS) were the primary outcome and secondary outcome in our study, respectively. We also assessed difference on the hazard ratio (HR) between European and North American groups. Results A total of 14 randomized clinical trials including 9387 patients were finally eligible for meta-analysis in our study. With respect to the pooled HR in treatment with PD-1/L1 inhibitors, North American patients presented OS as 0.60 (95% CI 0.53 to 0.67), and PFS as 0.49 (95% CI 0.40 to 0.59), whereas European patients presented OS as 0.76 (95% CI 0.62 to 0.90), and PFS as 0.58 (95% CI 0.44 to 0.72), relative to their corresponding control groups. OS efficacy thus varied significantly (P heterogeneity  = 0.028) between North American and European patients when treated with PD-1/L1 inhibitors. Conclusions Our findings were very surprising especially considering the higher prevalence of cancer in Europe. Although PD-1/L1 inhibitors improved OS and PFS in both North American and European patients compared with controls, the magnitude of benefit was region-dependent. North American patients can benefit more from PD-1/L1 inhibitors than European patients. More researches were urgently demanded to explore its potential molecular mechanisms.