The effects of race on anti-PD-(L)1 monoclonal antibodies in non-small cell lung cancer: A systematic literature review and meta-analysis

Introduction: Non-small cell lung cancer (NSCLC) represents approximately 85 % of lung cancers, with five-year survival only 4.5 % for metastatic disease. Programmed death (ligand)-1 (PD-[L]1) inhibitors have advanced NSCLC treatment, but patient demographics can potentially affect clinical outcomes. This systematic literature review and meta-analysis were undertaken to determine if the benefits of anti-PD-(L)1 therapies in NSCLC are independent of race (bio-geographic background). Methods: PubMed, Embase, Cochrane Library and World Health Organization Global Index Medicus were systematically searched (inception-to-Aug-2024). Primary analysis focused on studies with subgroup analysis (White vs Asian, White vs Non-White, Asian vs Non-Asian) of anti-PD-(L)1 efficacy in both resectable/localized and unresectable/advanced NSCLC. Subgroup analysis included stratification by PD-L1 expression, treatment line, and treatment regimen. Bayesian inferential meta-analysis was performed for outcomes with ≥ 1 study. Results: From 4406 records, 22 randomized controlled trials, 3 pooled analyses, and 2 pharmacokinetic studies were included. In unresectable/advanced NSCLC, anti-PD-(L)1 therapy significantly improved overall survival and progression-free survival (PFS) for White (hazard ratio [HR] 0.80; 95 % credible interval [95 % CrI] 0.74–0.87, p < 0.001 and HR 0.68; 95 % CrI 0.61–0.77, p < 0.001, respectively) and Asian (HR 0.81; 95 % CrI 0.69–0.96, p = 0.027 and HR 0.63; 95 % CrI 0.50–0.80, p = 0.002) patients. The significant improvements in PFS were maintained for both groups within all sub-analyses. Limited data prohibited conduction of meta-analysis for resectable/localized NSCLC. Conclusions: The benefits of anti-PD-(L)1 therapy in unresectable/advanced NSCLC appear similar for White and Asian patients. Increased quality and quantity of data is required to draw definitive conclusions for resectable/localized NSCLC and with respect to treatment line/regimen and PD-L1 expression.