Comparative efficacy and safety of immunotherapies targeting the PD-1/PD-L1 pathway for previously treated advanced non-small cell lung cancer: A Bayesian network meta-analysis

Abstract

Background: Two PD-1 (pembrolizumab, nivolumab) and one PD-L1(atezolizumab) inhibitors are approved for previously treated advanced non-small cell lung cancer but have not been compared in head-to-head trials.

Method: A network meta-analysis was conducted to compare efficacy/safety of PD-1/PD-L1 inhibitors.

Results: In five-trials (including long-term updates) with docetaxel as common comparator there were no differences in OS and PFS between PD-1/PD-L1 inhibitors. Pembrolizumab (odds ratio(OR) = 2.22, 95%CrI = 1.28-3.70) and nivolumab (OR = 1.92, 95%CrI = 1.15-3.23) had higher ORRs than atezolizumab and at PD-L1 expression ≥50% and ≥1%. Probabilistically, pembrolizumab ranked first in OS and ORR, and in OS sub-analyses for adenocarcinoma, EGFR-mutant, ECOG-score-1, male, and age <65 years. Nivolumab ranked first in PFS, and in OS sub-analyses for squamous-cell disease, EGFR-wild-type, and ECOG-score-0. Pembrolizumab and nivolumab ranked the best option for most of adverse events.

Conclusion: While pembrolizumab and nivolumab prevailed in rank in OS and ORR benefit, patient characteristics, safety and tolerance should be considered in treatment decision-making.

Keywords: Atezolizumab; Immunotherapy; Network meta-analysis; Nivolumab; Pembrolizumab.