Immune checkpoint inhibitors’ (ICI) efficacy according to PD-L1 expression for advanced or metastatic NSCLC: Systematic review and meta-analysis.

e21723 Background: Blocking PD-1 pathway has become a milestone in treating many tumors, including non-small cell lung cancer (NSCLC) for first and second line therapies. Although their benefits for some patients, these drugs are not full available in developing countries due to high treatment cost. In this study, we assessed the efficacy of five PD-1 or PD-L1 blockers (nivolumab, pembrolizumab, atezolizumab, durvalumab and avelumab), associated or not to chemotherapy, according to PD-L1 expression. Methods: We performed a systematic review and meta-analysis of randomized clinical trials in the databases MEDLINE/Pubmed, EMBASE, COCHRANE Library and LILACS up to November 2018. We selected trials comparing ICI alone, or associated with ICI or chemotherapy, versus chemotherapy or placebo. Primary outcome was overall survival (OS) and secondary outcome was progression free survival (PFS). Risk of bias of included trials was assessed by Cochrane’s recommended tool and data meta-analysis was performed by Review Manager V5.3 software. Results: We assessed OS and PFS of 12 trials in our meta-analysis. The methodological quality was considered moderate according to Cochrane’s tool. The pooled hazard ratio were 0.70 (95% CI 0.63, 0.78; p < 0.01; I² = 58%) for OS and 0.75 (95% CI 0.64, 0.89; p < 0.01; I² = 88%) for PFS. Subgroup analysis for PD-L1 < 1%, ≥ 1% and ≥ 50% showed OS of 0.78 (95% CI 0.64, 0.95; p = 0.09; I² = 46%), 0.69 (95% CI 0.59, 0.81; p < 0.01; I² = 79%) and 0.57 (95% CI 0.48, 0.68; p = 0.10; I² = 40%), respectively. Data for PFS were 0.85 (95% CI 0.71, 1.03; p = 0.21; I² = 31%), 0.77 (95% CI 0.64, 0.92; p < 0.01; I² = 83%) and 0.53 (95% CI 0.46, 0.62; p = 0.14; I² = 36%), respectively. Conclusions: Our data suggest a dose-response relationship between PD-L1 level and survival outcomes. It was not possible to conduct our meta-analysis by median OS and median PFS difference once these data were not available for every trial we selected. Considering the high price of immune therapy and budget limitations in developing countries’ health system, our findings could optimize health technology assessment agencies recommendations for treating NSCLC with high expression of PD-L1.