Meta-analysis of long-term survival by number of immune checkpoint inhibitors in PD-L1-negative metastatic non-small cell lung cancer

With multiple frontline immune checkpoint inhibitor (ICI) treatment regimens availabel, the optimal treatment for patients with PD-L1 negative metastatic non-small cell lung cancer has yet to be defined. A systematic review and meta-analysis of six phase 3 randomized controlled trials (RCTs, n=1684 PD-L1 negative patients), published from 2022 to 2024, investigated overall survival (OS) and progression-free survival (PFS) with various ICI regimens plus chemotherapy versus chemotherapy alone. Patients who received ICIs exhibited superior OS and PFS compared with those who did not. Doublet ICI had a lower HR for OS than single-agent ICI, but these differences were not statistically significant. PFS was not different bewteen the doublet ICI and the single ICI subgroup. Stratifying by histological subtype, 3 RCTs of patients with squamous cell lung cancer were analyzed. Doublet ICI, but not singlet ICI, plus chemotherapy was associated with improved OS. In contrast, patients with nonsquamous histological subtypes attained similar OS benefits from either doublet or singlet ICI.