2475 - Impact of PDL-1 Expression on Long Term Disease Outcomes in Unresectable Locally Advanced Non-Small-Cell Lung Cancer Treated with Chemoradiation with or without Immunotherapy

Purpose/Objective(s): Programmed death ligand-1 (PD-L1) expression plays an important role in tumor cells avoiding immune detection and has influenced individualized non-small cell lung cancer (NSCLC) treatment. We explored the role of PD-L1 expression on oncological outcomes in locally advanced NSCLC treated with chemoradiation with or without PD(L)1 immunotherapy (IO) to identify its role as a predictive biomarker.

Materials/Methods: 182 patients with locally advanced NSCLC treated between 2009 and 2024 were retrospectively evaluated. All patients had unresectable NSCLC and received definitive CRT, and 45% (n=82) patients did receive IO. We stratified patients based on their PD-L1 status [23 patients (12.6%) were PD-L1 negative, and 39 patients (21.4%) were PD-L1 positive, 120 patients (65.9%) had unknown PD-L1 status]. Progression free survival (PFS) and overall survival (OS) were evaluated by Kaplan-Meier analysis, with log-rank test for subgroup analysis.

Results: The median age was 66 years [IQR 58.7-75]. 51.1% (n=93) patients were females while 72.5% (n=132) were former smokers and 14.8% (n=27) were current smokers. 89.6% (n=163) had ECOG PS 0-1. Adenocarcinoma was the most common histology (n=96; 52.7%) followed by squamous cell carcinoma (n=72; 39.6%) and mixed histology (7.7%; n=14) . Stage III disease was present in 163 patients (89.5%), while stage IIB was present in 19 patients (10.5%). The median duration of follow-up was 30 months. Median PFS and OS of the entire cohort was 13 months and 38 months, respectively. Patients receiving IO had statistically significant better median PFS than patients who did not received IO (20 vs 10 months; p=0.047) and better OS (55 vs 27 months; p<0.01). PDL1 positive status showed a trend towards better OS (Median – not reached vs 54 months; p=NS) as compared to PDL1 negative patients. In patients with PDL1 negative status, IO did not impact OS. In PDL1 positive patients, IO with CRT showed a trend towards better 5 yr OS (51% vs 42% p=NS) vs CRT alone. Multivariate analysis showed ECOG PS and IO use as significant prognostic factors for OS.

Conclusion: PD-L1 itself is a predictive biomarker in locally advanced NSCLC irrespective of IO use, with PD-L1 positive patients deriving the most survival benefit from adding immunotherapy to standard chemoradiation. These results demonstrate the role of molecular profiling and addition of immunotherapy in unresectable locally advanced NSCLC patients. More prospective studies are warranted to provide validation for the prognostic and therapeutic indications of PD-L1 expression.