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The combination of programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors with chemotherapy has emerged as a promising therapeutic option for advanced non-small-cell lung cancer (NSCLC). The aim of this meta-analysis was to evaluate the efficacy of the combined strategy in this setting. For this purpose, we performed a literature search of randomized controlled trials comparing PD-(L)1 inhibitors plus platinum-based chemotherapy versus chemotherapy alone in stage IV NSCLC patients. Seven clinical trials with 4562 patients were included. In the intention-to-treat wildtype population, PD-(L)1 inhibitor plus chemotherapy was significantly associated with improved progression-free survival (PFS) (Hazard ratio (HR) = 0.61, 95% confidence interval (CI): 0.57-0.65, p &lt; 0.001) and overall survival (OS) (HR = 0.76, 95% CI: 0.67-0.86; p &lt; 0.001) compared to chemotherapy. A significantly higher overall response rate (ORR) was also observed with the combined strategy (Odds ratio (OR) = 2.12, 95% CI: 1.70-2.63, p &lt; 0.001). Furthermore, in all the analyzed subgroups, addition of PD-(L)1 inhibitors to chemotherapy significantly improved efficacy endpoints. Specifically, stratification according to PD-L1 expression revealed a benefit across all patients, regardless of their PFS status. In conclusion, PD-(L)1 blockade added to standard platinum-based chemotherapy significantly improved PFS, OS, and ORR in the up-front treatment of advanced NSCLC.

PD-(L)1 Inhibitors in Combination with Chemotherapy as First-Line Treatment for Non-Small-Cell Lung Cancer: A Pairwise Meta-Analysis