Real-World Evidence That Non-Smokers With High PD-L1 Non-Squamous NSCLC Have Poorer Outcomes With Immune Checkpoint...

Area of Science:

• Oncology
• Immunotherapy
• Thoracic Cancers

Background:

• Immune checkpoint inhibitors (ICIs) are effective for non-small cell lung cancer (NSCLC) with high PD-L1 expression.
• Biomarkers beyond PD-L1 for ICI efficacy are limited.
• The role of smoking-related immune activation in non-squamous NSCLC, particularly in non-smokers, requires further investigation.

Purpose of the Study:

• To investigate the impact of smoking status on the efficacy of ICI-based treatments in patients with high PD-L1 non-squamous NSCLC.
• To identify potential predictive biomarkers beyond PD-L1 expression.

Main Methods:

• Retrospective analysis of 74 patients with Stage IIIB-IV non-squamous NSCLC and PD-L1 ≥ 50% without EGFR/ALK/ROS1 mutations.
• Stratification of patients based on smoking status (smokers vs. non-smokers).
• Evaluation of treatment response (RECIST v1.1), progression-free survival (PFS), and overall survival (OS) using Kaplan-Meier and Cox regression.

Main Results:

• Smokers (72.9%) exhibited significantly higher partial response rates (66.7% vs. 25.0%), longer median PFS (12.8 vs. 1.4 months), and improved OS (47.1 vs. 10.0 months) compared to non-smokers.
• In non-smokers, chemoimmunotherapy significantly improved PFS over ICI monotherapy (not reached vs. 1.4 months).
• Multivariate analysis confirmed smoking as an independent predictor of better PFS (HR=0.234) and OS (HR=0.229).

Conclusions:

• Non-smokers with PD-L1-high non-squamous NSCLC demonstrate poorer outcomes with ICI monotherapy.
• Chemoimmunotherapy may be a preferred treatment option for non-smokers in this cohort.
• Smoking history serves as a simple, clinically relevant factor for stratifying patients in ICI-based treatment decisions.