High-Grade Pneumonitis Events in Patients With Unresectable, Locally Advanced NSCLC Treated With Definitive Chemoradiation Followed by Adjuvant Durvalumab.

Background: The standard of care for unresectable locally advanced NSCLC is concurrent chemotherapy and radiation (CRT) followed by adjuvant durvalumab, established by the PACIFIC trial, which revealed acceptable although higher rates of pneumonitis with durvaluamb than placebo. We retrospectively reviewed patients with locally advanced NSCLC from 2018 to 2022 treated with definitive CRT (≥60 Gy) followed by at least one dose of adjuvant durvalumab. Objective: To review the incidence of pneumonitis and contributing factors, and also to review grade 5 pneumonitis (G5) events. Methods: We identified 78 cases with a median age of 70.0 years and a median follow-up of 36 months. All patients received CRT of at least 60 Gy at 2 Gy per fraction. A total of 22 patients (28.2%) completed 12 months of durvalumab. The cumulative incidence of any-grade pneumonitis was 28.2%. Pneumonitis rate in grades 1, 2, 3, 4, and 5 was 1.3%, 10.3%, 7.7%, 0.0%, and 9.0%, respectively. Results: Multivariate analysis did not reveal significant factors associated with G5 pneumonitis. There were 8 patients who received radiation therapy doses above standard limits and, of these, only two developed G5 pneumonitis. All patients with G5 pneumonitis had multiple comorbidities or previous malignancy treated with systemic therapy. The median overall survival was 31.1 months and the median progression-free survival was 12.7 months. Conclusions: We report comparable overall rates of pneumonitis relative to published data with higher rates of G5 pneumonitis. Patients with high-dose radiation therapy (≥60 Gy) and Eastern Cooperative Oncology Group performance status greater than or equal to 2 may tolerate adjuvant durvalumab, though providers should exercise caution in patients with extensive comorbidities.