Evaluation of the incidence of pneumonitis in United States veterans with non-small cell lung cancer receiving durvalumab following chemoradiation.

Abstract

9034 Background: Locally advanced, unresectable non-small cell lung cancer is commonly treated with concurrent chemoradiation therapy (CRT). Durvalumab is a PD-L1 immune checkpoint inhibitor (ICI) administered following completion of CRT. Pneumonitis is a known toxicity of ICI therapy. In the landmark PACIFIC study the incidence of pneumonitis in patients receiving durvalumab was 33.9% (any grade) and 3.4% (grade 3/4) compared to placebo 24.8% and 2.6% ( Antonia et al, NEJM 2017). The incidence of pneumonitis is thought to be higher in real-world populations. This study evaluated the incidence of pneumonitis in a cohort of U.S. Veterans. Methods: Durvalumab recipients were identified using VA Informatics and Computing Infrastructure databases. Using pharmacy records we confirmed durvalumab and corticosteroid prescriptions. Clinical information was obtained via the electronic medical record. The primary outcome was the development of pneumonitis. We defined asymptomatic pneumonitis as the presence of new radiographic findings consistent with pneumonitis without documented clinical symptoms. We recorded pneumonitis grade as reflected in clinical documentation. If not specifically graded, we used Common Terminology Criteria for Adverse Events (CTCAE v4.0) to assess severity. Logistic regression analysis evaluated associations between pneumonitis and age, comorbidities, radiation dose and stage. Cox proportional hazards analysis evaluated associations between pneumonitis and risk of death. Results: A total of 123 veterans received durvalumab through 3/31/2019 (with follow up through 11/15/2019). Asymptomatic radiographic infiltrates occurred in 49 (39.8%) patients. There were 26 cases of clinically important pneumonitis Grade 2: 9(7.3%), Grade 3: 14 (11.4%), Grade 4: 2(1.6%), and grade 5: 1 (.08%). Acute hypersensitivity reactions occurred in five (4.1%) patients. Reported reasons for discontinuation of durvalumab included: disease progression [38 (31%)], toxicity [30 (24.3%)], and patient death [1 (1.6%)]. There was no association between age, time from radiation end to durvalumab initiation, radiation dose, smoking history, chemotherapy used or disease stage on development of pneumonitis. Cox analysis did not demonstrate an association between pneumonitis and risk of death. Conclusions: Clinically significant pneumonitis was more frequent in this cohort than reported in prior clinic trial populations. Further studies to identify pneumonitis risk factors are needed.