Which treatment is preferred for advanced non-small-cell lung cancer with wild-type epidermal growth factor receptor in second-line therapy? A meta-analysis comparing immune checkpoint inhibitor, tyrosine kinase inhibitor and chemotherapy

Background: The recommendations regarding the optimum treatment for advanced non-small-cell lung cancer (NSCLC) patients with wild-type (WT) epidermal growth factor receptor (EGFR) tumors remain unclear. This meta-analysis was conducted to assess the efficacy among programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1) antibody, EGFR-tyrosine kinase inhibitors (TKI) and chemotherapy in second-and third-line therapy. Patients and methods: Randomized trials investigating two of the three treatments were searched and included. Multiple treatments comparison and pairwise comparison were performed to assess overall survival (OS) and progression-free survival (PFS), expressed as hazard ratios (HRs). The effect of prespecified study-level characteristics was assessed by subgroup analysis and meta-regression. Results: 12 randomized trials accruing 3341 advanced patients with WT EGFR tumors were analyzed. PD-1/PD-L1 antibody was associated with significantly longer OS and PFS than chemotherapy (OS: HR 0.67, 95% CrI 0.60-0.75; PFS: HR 0.83, 95% CrI 0.73-0.95) and TKI (OS: HR 0.59, 95% CrI 0.50-0.70; PFS: HR 0.75, 95% CrI 0.66-0.84), while chemotherapy was associated with significantly longer OS (HR 0.88, 95% CrI 0.77-0.99) and PFS (HR 0.75, 95% CrI 0.66-0.84) than TKI. Conclusions: For advanced NSCLC patients with WT-EGFR tumors in second- or third-line therapy, PD-1/PD-L1 antibody appeared to be the most efficacious treatment, which was followed by chemotherapy. EGFR-TKI was worse than chemotherapy.