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.