3553 - Survival Outcomes in Inoperable Stage III NSCLC: Comparing Immunotherapy (+/- Chemotherapy) followed by Radiotherapy vs. Standard of Care Chemoradiation Followed by Adjuvant Durvalumab
Presenter(s)
M. T. Mahoney1, H. Sivaraju2, J. Fredette3, L. Zhang1, M. J. Edelman4, and S. S. Kumar5; 1Fox Chase Cancer Center, Philadelphia, PA, 2Philadelphia College of Osteopathic Medicine, Philadelphia, PA, 3Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, PA, 4Division of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, 5Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA
Purpose/Objective(s): There is growing interest in optimizing the sequencing of PD-1/PD-L1 checkpoint inhibitor immunotherapy +/- chemotherapy (CKI+/- CT) followed by platinum-based chemoradiation (chemoRT) for the treatment of patients with unresectable locally advanced Stage III non-small cell lung cancer (LA-NSCLC). Our goal was to compare the two approaches: CKI (+/- CT) before radiation (RT) (CKI(+/-CT >RT) to the current SOC of post-RT using a well curated national database.
Materials/Methods: A retrospective comparison of LA-NSCLC patients that received CKI followed by definitive chemoRT or RT alone (CKI+/- CT>RT) versus the standard of care (SOC) of chemoRT then adjuvant durvalumab was conducted using the Flatiron Health Research Database. The primary endpoint was overall survival (OS) with a secondary endpoint of recurrence-free survival (RFS) defined as time from start of therapy to recurrent disease (locoregional or distant) or death from any cause. Survivals were compared with log-rank tests, and multivariable Cox proportional hazards regression.
Results: There were 57 patients who received CKI (+/- CT)>RT and 869 patients who received SOC from March 31, 2017 to June 30, 2025. The groups were well balanced in terms of demographic factors. The median age was 70. Over 80% of patients had ECOG status 0-1. Most patients were Stage IIIA - 93% (CKI(+/- CT)>RT) and 90% (SOC). There was an even split between squamous cell carcinoma and non-squamous cell histology in both groups. The median duration of CKI(+/- CT)>RT was 46 days. The median OS was 22 months (95%CI 20-NA) for CKI(+/- CT)>RT and 31 months for SOC (95%CI 28-35). Multivariable analysis found CKI(+/- CT)>RT cohort to be numerically, but not significantly inferior (HR 1.3, p = 0.19). RFS for CKI(+/- CT)>RT vs. SOC was 17 months (95%CI 12-26) vs and 24 months (95%CI 20-26), respectively. Multivariable analysis found a trend towards inferior RFS for CKI(+/- CT)>RT vs. SOC (HR 1.3, p = 0.17).
Conclusion: Our study offers real-world insights into how treatment sequencing influences outcomes and contributes to efforts to optimize care for patients with unresectable locally advanced Stage III non-small cell lung cancer. This report is limited by its retrospective nature and the small size of the CKI(+/-CT)>RT cohort relative to SOC. Neither initial nor consolidation immunotherapy was clearly superior and prospective trials are indicated.