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.