A pooled meta-analysis of PD-1/L1 inhibitors incorporation therapy for advanced non-small cell lung cancer

Objective: Immune checkpoint inhibitors, especially the programmed cell death receptor-1/ligand 1 (PD-1/L1) inhibitors, displayed promising efficacy in non-small cell lung cancer (NSCLC) patients. Incorporation of anti-PD-1/L1 antibodies into other therapeutic regimens (including CTLA-4 inhibitors, chemotherapy, EGFR-TKIs and IDO inhibitors) is currently in active clinical research. This meta-analysis summarized recent developments in four combination regimens of PD-1/L1 inhibitors. Methods: We searched PubMed, the Cochrane Library and the Embase database up to July 2018, on the combination therapy of PD-1/L1 inhibitors in NSCLC patients. Results: Seventeen trials were finally included in the current meta-analysis. The combined objective response rates (ORR) for PD-1/L1 inhibitors in combination with CTLA-4 inhibitors, chemotherapy, EGFR-TKIs, and IDO inhibitors were 32% (19%–44%), 49% (46%–53%), 55% (28%–83%) and 35% (20%–50%) respectively. The combined ORR for first line PD-1/L1 inhibitors combination with CTLA-4 inhibitors, chemotherapy, and EGFR-TKIs were 35% (17%–53%), 51% (46%–56%) and 43% (−7%–93%) respectively, and the combined ORR in the second or more line setting were 36% (8%–65%), 17% (−13%–46%), 39% (19%–59%) and 35% (20%–50%) respectively. The pooled 6-month progression-free survival rate (6m PFSr) and 1-year overall survival rate (1y OSr) for combination therapy of PD-1/L1 inhibitors with CTLA-4 inhibitors or chemotherapy were 35% or 65% (6m PFSr) and 31% or 70% (1y OSr) respectively. Anti-PD-1/L1 drugs combined with anti-CTLA-4 drugs exhibited a more potent efficacy on PD-L1 positive patients (OR=0.33, 95%CI: 0.12–0.88). This trend was not observed in patients receiving combination therapy of PD-1/L1 inhibitors with chemotherapy (OR=0.96, 95%CI: 0.51–1.78). Conclusion: The included four combination regimens were potential treatment strategies and well tolerated for NSCLC patients. Further, the therapy lines and PD-L1 expression status were correlated with treatment efficacy. Keywords: PD-1/L1 inhibitors, combination therapy, meta-analysis, non-small cell lung cancer