Comparative efficacy and safety of PD-1/PD-L1 immunotherapies for non-small cell lung cancer: a network meta-analysis.

OBJECTIVE: PD-1/PD-L1 inhibitors are a relatively new class of immunotherapeutic drugs approved for advanced non-small-cell lung cancer. The purpose of this study was to conduct a network meta-analysis to compare the safety and efficacy of these immune checkpoint inhibitors (ICIs). MATERIALS AND METHODS: We used Bayesian network meta-analysis methods to evaluate the efficacy and safety of the included treatments. We further analyzed subgroups based on PD-L1 expression level, histology type, and line of the treatment setting. RESULTS: We identified 19 RCTs, including 12,753 patients. In the analysis of all-comers, the pembrolizumab/chemotherapy combination ranked best for overall survival (OS) and progression-free survival (PFS). Durvalumab was the only ICI treatment that showed no benefit over chemotherapy. In the first-line setting only, in terms of OS, atezolizumab, pembrolizumab/chemotherapy, and nivolumab/ipilimumab ranked as the best treatments for patients with PD-L1 expression levels of ≥50%, 1-49%, and <1%, respectively. Nivolumab, atezolizumab, pembrolizumab, and durvalumab all had lower odds of grade 3 or greater treatment-related adverse events (TRAEs) compared to chemotherapy. With the addition of chemotherapy to any ICI regimen, the odds of TRAEs increased in a considerable and statistically significant way. CONCLUSIONS: While the pembrolizumab/chemotherapy combination was the most effective therapy in the overall cohort of all-comers, treatment preferences varied by treatment-line setting, tumor characteristics, and outcome of interest. In the first-line setting, the most effective treatments for patients with PD-L1 expressions of ≥50%, 1-49%, and <1% were atezolizumab, pembrolizumab/chemotherapy, and nivolumab/ipilimumab, respectively.