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