Comparison of atezolizumab, durvalumab, pembrolizumab, and nivolumab as first-line treatment in patients with extensive-stage small cell lung cancer: A systematic review and network meta-analysis

BACKGROUND: In recent years, immune checkpoint inhibitors (ICIs) including atezolizumab, durvalumab, pembrolizumab, and nivolumab have reported their efficacy and safety profile in patients with extensive-stage small cell lung cancer (ES-SCLC). However, given the diverse efficacy and inconsistent safety among the ICIs, with the absence of head-to-head researches designed to evaluate the efficacy among them, it might bring with confusion on selection in clinical practice. OBJECTIVES: The present systematic review and network meta-analysis was performed to conduct indirect comparisons on efficacy and safety profile among ICIs, including atezolizumab, durvalumab, pembrolizumab, and nivolumab as first-line treatment in patients with ES-SCLC. DESIGN: Several databases were retrieved with established criteria until June 20, 2020, with the main MeSH Terms and their similarities. Hazard ratios of overall survival (OS) and progression-free survival (PFS), odds ratios (ORs) of disease control rate (DCR), objective response rate (ORR), and adverse events (AEs) were compared indirectly with network meta-analysis. DATA SOURCES: Medline, Cochrane library, and Embase. ELIGIBILITY CRITERIA: Prospective, randomized, controlled clinical studies, which reported PFS, OS, and AEs. DATA EXTRACTION AND SYNTHESIS: Clinical characteristics were extracted by the 2 authors independently. Comparisons of HRs were calculated for PFS and OS by random effect model. ORR, DCR, and AEs were presented with ORs. Based on surface under the cumulative ranking curve, and forest plots, efficacy and safety of the treatments were ranked, with predicted histogram described. RESULTS: In total, there were 4 studies including 1547 patients who met the eligibility criteria and enrolled. For indirect comparisons, no significant difference on PFS was observed between atezolizumab and durvalumab (HR 0.96, 95% CI, 0.72–1.29), or between atezolizumab and pembrolizumab (HR 1.05, 95% CI, 0.78–1.43), or between atezolizumab and nivolumab (HR 1.18, 95% CI, 0.79–1.79), or between durvalumab and pembrolizumab (HR 1.10, 95% CI, 0.84–1.43). or between durvalumab and nivolumab (HR 1.23, 95% CI, 0.83–1.82), or between pembrolizumab and nivolumab (HR 1.12, 95% CI, 0.76–1.66), nor significant difference on OS observed between atezolizumab and durvalumab (HR 0.93, 95% CI, 0.67–1.30), or between atezolizumab and pembrolizumab (HR 0.88, 95% CI, 0.62–1.24), or between atezolizumab and nivolumab (HR 1.04, 95% CI, 0.66–1.66), or between durvalumab and pembrolizumab (HR 0.94, 95% CI, 0.70–1.25), or between durvalumab and nivolumab (HR 1.12, 95% CI, 0.73–1.71), or between pembrolizumab and nivolumab (HR 1.19, 95% CI, 0.77–1.84). However, durvalumab was shown statistical superiority on ORR when compared with atezolizumab (HR 0.79, 95% CI, 0.64–0.98), also with significantly higher risk on immune-related AEs when compared with atezolizumab (OR 0.22, 95% CI, 0.10–0.50), and pembrolizumab (OR 3.12, 95% CI, 1.27–7.64). CONCLUSIONS: Results of the study revealed that there was no statistical difference on PFS or OS among agents of atezolizumab, durvalumab, pembrolizumab, and nivolumab as first-line treatment in patients with ES-SCLC. However, durvalumab was shown superiority on ORR when compared with atezolizumab, also with significantly higher risk on immune-related AEs.