3556 - Real-World Prognostic Impact of PD-L1 Status in Unresectable NSCLC Treated with Concurrent Chemoradiation and Consolidative Immunotherapy
Presenter(s)
L. Martinka1, K. Shin2, K. Olabode1, Simran3,4, J. Gray5, S. Puri5, A. N. Saltos5, T. Tanvetyanon5, B. Creelan5, A. Chiappori5, C. Lu5, M. Shafique5, S. A. Rosenberg1, S. K. Jabbour6, T. J. Dilling1, and J. Kim7,8; 1Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 2Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 3Department of Radiation Oncology, All India Institute of Medical Sciences (AIIMS), New Delhi, India, 4Moffitt Cancer Center, Tampa, FL, 5Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 6Department of Radiation Oncology, Rutgers Cancer Institute, New Brunswick, NJ, 7Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL, 8Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Purpose/Objective(s):
Programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) is routinely assessed in non–small-cell lung cancer (NSCLC). However, its prognostic and predictive significance in unresectable locally advanced disease treated with definitive chemoradiation followed by consolidation immunotherapy per the PACIFIC regimen remains incompletely defined. We hypothesized that PD-L1 expression would be associated with differential survival outcomes in patients receiving the PACIFIC regimen.Materials/Methods:
Patients with histologically confirmed unresectable stage IIB-IIIC NSCLC treated with the PACIFIC regimen from 2015 to 2024 were retrospectively identified. Of 263 patients, 127 had PD-L1 scores available – these patients were stratified by PD-L1 status. Clinical variables collected included demographics, disease, and treatment characteristics. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared using the log-rank test. Secondary analysis was performed using univariable and multivariable Cox proportional hazards regression models to identify independent prognostic factors.Results:
A total of 127 patients were included, with 49 being PD-L1 negative (N; TPS < 1%), 44 being PD-L1 intermediate (I; TPS 1-49%), and 34 being PD-L1 high (H; TPS = 50%). The median follow-up was 45.3 months (range: 0.87 – 93.33). The median age was 69 years (39-87). 48.4% were female, 47.7% (n=61) were former smokers and 30.5% (n=39) were current smokers. 123 patients were stage III (96.1%). Adenocarcinoma was the most common histology (n=61; 47.7%), followed by squamous cell carcinoma (n=41; 32%). Median radiation dose was 6000 cGy (6000-7000). The most common chemotherapy regimen was Paclitaxel/Carboplatin (n=99; 77.3%). The median OS for N, I, and H cohorts were 27.5 months (95% CI 24.9-55.5), 75.7 months (95% CI 31.7-NA), and not reached, respectively (p = 0.025). The median PFS for N, I, and H cohorts were 15.3 months (95% CI 12.9-27), 51.4 months (95% CI 32-NA), and not reached, respectively (p = 0.010). In multivariable analysis, including PD-L1 status and clinicopathologic variables, only PD-L1-negative status was independently associated with OS (HR 2.50; 95% CI 1.19-5.22; p = 0.015) and PFS (HR 2.74; 95% CI 1.34-5.63; p = 0.006).Conclusion:
PD-L1 expression functions as a critical predictive biomarker in NSCLC, reflecting its biological role in immune evasion and guiding selection of immunotherapy. In our cohort treated with the PACIFIC regimen, increasing PD-L1 TPS was associated with progressively improved OS and PFS, with the greatest benefit observed in patients with high expression (>50%), followed by intermediate (1–49%) tumors. These findings further support PD-L1 as a clinically meaningful stratification tool in the consolidative immunotherapy setting.