High-grade Pneumonitis Events in Unresectable, Locally Advanced Non-Small Cell Lung Cancer Patients Treated with Definitive Chemoradiation followed by Adjuvant Durvalumab

The standard of care for unresectable locally advanced non-small cell lung cancer (LA-NSCLC) is concurrent chemotherapy and radiation (CRT) followed by adjuvant durvalumab, established by the PACIFIC trial which showed acceptable although higher rates of pneumonitis with durvaluamb than placebo. We retrospectively reviewed LA-NSCLC patients between 2018-2022 treated with definitive CRT (≥ 60 Gy) followed by at least one dose of adjuvant durvalumab. The primary objective was to review the incidence of pneumonitis, contributing factors, and review G5 pneumonitis events. We identified 78 cases with median age of 70.0 years and median follow up of 36 months. All patients received ≥ 60 Gy CRT at 2 Gy per fraction. Twenty-two patients (28.2%) completed twelve months of durvalumab. The cumulative incidence of any grade pneumonitis was 28.2%. Pneumonitis rate by grade 1, 2, 3, 4, and 5 was 1.3%, 10.3%, 7.7%, 0.0%, and 9.0%, respectively. Multivariate analysis did not reveal significant factors associated with G5 pneumonitis. Eight patients received RT doses above standard limits and, of these, only two developed G5 pneumonitis. All patients with G5 pneumonitis had multiple comorbidities and/or prior malignancy treated with systemic therapy. The median OS (overall survival) was 31.1 months and median progression-free survival (PFS) was 12.7 months. We report comparable overall rates of pneumonitis relative to published data with higher rates of G5 pneumonitis. Patients with HDRT (high dose radiation therapy ≥ 60 Gy) and PS (ECOG performance status) > 2 may tolerate adjuvant durvalumab, although providers should exercise caution in patients with extensive comorbidities.