Comparative efficacy and safety of first-line treatments for advanced non-small cell lung cancer with immune checkpoint inhibitors: A systematic review and meta-analysis.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the predominant type of lung cancer, and most clinically curable patients are diagnosed with locally advanced disease. Although the efficacy of standard platinum-based chemotherapy doublets is relatively limited. The effect of immune checkpoint inhibitors (ICIs) remains controversial, and its role in the first-line treatment of advanced NSCLC is obscure. Thus, we carried out a systematic review and meta-analysis to compare the efficacy and safety of ICIs for advanced NSCLC. METHODS: The PubMed, Cochrane Central Register Trial, and American Society of Clinical Oncology databases were searched from inception to 30 April 2018. We searched for randomized controlled trials comparing single-agent programmed cell death protein 1/programmed death-ligand 1 inhibitors (nivolumab, pembrolizumab, or atezolizumab) or cytotoxic T-lymphocyte-associated antigen 4 inhibitor (ipilimumab) with chemotherapy in NSCLC patients. Progression-free survival, overall survival, objective response rate, and adverse events were pooled for meta-analysis by Review Manager (RevMan version 5.3) software. RESULTS: After exclusion of ineligible studies, 12 eligible randomized controlled trials were included. Data showed that ICIs significantly improved progression-free survival (HR 0.66, 95% CI 0.57-0.77, P < 0.00001), overall survival (HR 0.77, 95% CI 0.64-0.91, P = 0.003), and but not objective response rate (RR 1.97, 95% CI 1.25-3.13, P = 0.004) in all unselected NSCLC populations. However, they failed to increase the OS of programmed death-ligand 1 = 1-49% subgroup (HR 0.78, 95% CI 0.51-1.19, P = 0.25) and PFS of programmed death-ligand 1<1% subgroup (HR 0.85; 95%CI 0.70 to 1.03, P=0.09) in ICIs+chemotherapy over chemotherapy. Meanwhile, OS of programmed death-ligand =1-49% subgroup (HR 0.92; 95%CI 0.77 to 1.10, P=0.36) and PFS of programmed death-ligand 1≥50% subgroup (HR 0.76; 95%CI 0.52 to 1.11, P=0.15) showed no significant differences in ICIs over chemotherapy. Furthermore, fewer adverse events were observed in the ICIs groups than control groups. CONCLUSION: ICIs are overall better tolerated than chemotherapy. Our results provide further evidence supporting the favorable risk/benefit ratio for ICIs.