Stratification by PD-L1 TPS in Advanced NSCLC With Low PD-L1 Expression for Optimizing Immunotherapy.

Area of Science:

• Oncology
• Immunotherapy
• Lung Cancer Research

Background:

• Optimal first-line treatment for advanced non-small-cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of 1-49% is not established.
• Stratification by PD-L1 TPS may refine treatment strategies for NSCLC.

Purpose of the Study:

• To compare the efficacy of dual nivolumab and ipilimumab therapy versus single-agent immune checkpoint inhibitor (ICI) therapy in first-line treatment for advanced NSCLC with PD-L1 TPS 1-49%.
• To evaluate overall survival (OS) and progression-free survival (PFS) based on PD-L1 expression levels.

Main Methods:

• Multicenter, retrospective, observational study.
• Compared nivolumab and ipilimumab (with/without chemotherapy) vs. chemotherapy with a single-agent ICI in advanced NSCLC (PD-L1 TPS 1-49%).
• Propensity score-matching was used to analyze overall survival in matched populations.

Main Results:

• In PD-L1 TPS 1-20% group, dual therapy showed superior median OS (not reached vs. 12.0 months) and PFS (11.5 vs. 6.9 months) compared to single-agent ICI.
• In PD-L1 TPS 21-49% group, dual therapy showed superior median OS (9.0 months vs. not reached) compared to single-agent ICI, though PFS was shorter (4.1 vs. 8.3 months).

Conclusions:

• Treatment efficacy in advanced NSCLC with PD-L1 TPS 1-49% may depend on specific PD-L1 expression levels (1-20% vs. 21-49%).
• Nivolumab and ipilimumab-based dual therapy appears more effective than single-agent ICI for advanced NSCLC with ultra-low PD-L1 expression (1-20%).