The optimal treatment for advanced non-small-cell lung cancer (NSCLC) with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of 1-49% remains unknown. Further stratification by PD-L1 TPS may lead to optimization of treatment.

We conducted a multicenter, retrospective, observational study to compare nivolumab and ipilimumab with/without chemotherapy (dual-therapy group) and chemotherapy with a single-agent immune checkpoint inhibitor (ICI) (single-therapy group) as the first-line therapy for advanced NSCLC with a PD-L1 TPS of 1-49%. The primary endpoint was overall survival in the propensity score-matched population.

A total of 139 patients were enrolled; 113 in the single- (81.3%) and 26 in the dual- (18.7%) therapy groups. In the population with PD-L1 TPS of 1-20%, after propensity score-matching was performed, the median overall survival was 12.0 months for the single-therapy group, but was not reached for the dual-therapy group (p=0.022). The median progression-free survival was 6.9 and 11.5 months, respectively (p=0.02). In the population with PD-L1 TPS of 21-49%, after propensity score-matching, the median overall survival was not reached for the single-therapy group, but was 9.0 months for the dual-therapy group (p=0.04), whilst corresponding median progression-free survival was 8.3 and 4.1 months (p=0.087).

The results of this study suggest that in patients with NSCLC, the optimal treatment regimen may differ between those with PD-L1 TPS of 1-20% and 21-49%; moreover, nivolumab and ipilimumab-based therapy may be more effective than chemotherapy with a single-agent ICI for treating advanced NSCLC with ultra-low PD-L1 expression, particularly in those with a PD-L1 TPS of 1-20%.