Real-world outcomes and immune and cardiopulmonary toxicities of durvalumab following concurrent chemoradiotherapy in non–small cell lung cancer.

Abstract

e20097 Background: Durvalumab consolidation following concurrent chemoradiotherapy (CCRT) has improved overall survival (OS) in locally advanced non–small cell lung cancer (NSCLC). Long-term real-world effects of consolidation of immunotherapy on outcomes, including aggregate risk of immune and cardiopulmonary events, remain unclear. Methods: We performed a retrospective analysis using the SEER-Medicare database (2013–2020). We employed propensity score matching for the cohort of NSCLC patients who had received durvalumab, where each patient was paired with a non-durvalumab receiving patient to ensure balance across selected covariates, including age, sex, race, stage, and Charlson comorbidity index (CCI). Immune-related adverse events (irAEs), and cardiopulmonary events were identified using claims-based definitions. Cox proportional hazards and Fine–Gray competing-risk models were applied. Results: In total, 3554 patients with NSCLC who received durvalumab were identified. After propensity matching, 2751 patients were included in each cohort. Durvalumab was associated with significantly prolonged median OS duration compared with no durvalumab (44.6 vs 25.0 months, P< 0.001), closely approximating survival outcomes reported in the PACIFIC trial (47.5 vs. 29.1 months).Durvalumab was associated with increased risks of irAEs, including pneumonitis (sHR 1.84, P< 0.001), hypothyroidism (sHR 1.82, P< 0.001, Hashimoto’s thyroiditis (sHR 2.68, P< 0.001), autoimmune hepatitis (sHR 3.62, P= 0.03), dermatitis (sHR 1.80, P= 0.02), and gastroenteritis/colitis (sHR 1.31, P< 0.001). The cumulative incidence of pneumonitis and hypothyroidism approached approximately 20% and 35% at three years, respectively, with pneumonitis occurring predominantly within 18 months, while increased risk of hypothyroidism continued to occur beyond two years. In contrast, durvalumab was associated with lower risks of cardiomyopathy (sHR 0.74, P= 0.003), heart failure (sHR 0.87, P= 0.005), acute respiratory failure (sHR 0.29, P< 0.001), and COPD exacerbation (sHR 0.78, P< 0.001). Racial differences in select irAEs were observed and warrant further investigation. Conclusions: In this large real-world analysis, durvalumab consolidation following CCRT was associated with substantial OS benefit in patients who received CCRT. While irAEs were increased, non-immune related cardiopulmonary outcomes were unexpectedly more favorable. The timing and burden of toxicities highlight the importance of early monitoring for pneumonitis and prolonged surveillance for endocrine irAEs.