Real-world outcomes of prolonged versus shorter duration pembrolizumab following chemoradiation in non–small cell lung cancer: A propensity-matched analysis.

e20636 Background: The optimal duration of pembrolizumab following chemoradiation in non–small cell lung cancer (NSCLC) remains uncertain in real-world practice. Current guidelines do not provide clear recommendations regarding treatment duration beyond clinical trial protocols, resulting in substantial variability in real-world practice. While extended immunotherapy exposure is commonly pursued, its association with improved survival and healthcare utilization outside clinical trials is incompletely characterized. We compared outcomes between patients receiving prolonged versus shorter durations of pembrolizumab using a large real-world database. Methods: We conducted a retrospective cohort study using the TriNetX U.S. large de-identified EMR database from 72 U.S. healthcare organizations, including adult patients with NSCLC who received chemoradiation followed by pembrolizumab. Patients were categorized into: Full-duration pembrolizumab (continued ≥12 months), and Short-duration pembrolizumab (discontinued earlier). Propensity score matching (1:1) was performed for age, sex, race, smoking history, and comorbidities. Primary outcome was overall mortality. Secondary outcomes included hospitalizations, critical care utilization, emergency department visits, palliative care use, and prolonged services. Kaplan–Meier and Cox proportional hazards models were applied. Results: After matching, 450 patients were included in each cohort with well-balanced baseline characteristics. Mortality: Full-duration: 37.1% Short-duration: 46.4% Risk difference: −9.4% (p = 0.005) Hazard ratio (HR): 0.67 (95% CI, 0.55–0.83) Median overall survival: Full-duration: 1505 days Short-duration: 791 days Log-rank p < 0.001 Hospitalizations, critical care, emergency visits, and palliative care were similar between groups. Prolonged services occurred less frequently in the full-duration group (HR 0.61, 95% CI 0.38–0.97). Conclusions: In this large real-world cohort, the longer duration of pembrolizumab following chemoradiation was associated with significantly improved overall survival without increased healthcare utilization. These findings support sustained immunotherapy exposure when clinically feasible and highlight the value of real-world evidence in informing treatment duration decisions. Clinical implications of this study: supports continuation of pembrolizumab beyond early discontinuation when tolerated, demonstration survival benefit without excess healthcare burden.