Pneumonitis Following Thoracic Radiotherapy in EGFR-Mutated Non-Small Cell Lung Cancer Receiving Osimertinib

Introduction: Pneumonitis is a clinically important toxicity associated with both osimertinib and thoracic radiotherapy (TRT) in patients with metastatic EGFR NSCLC. The objective of this study was to characterize the incidence, severity, and clinical features of pneumonitis in patients receiving TRT in close temporal association with osimertinib. Materials and Methods: A retrospective study of patients who received both osimertinib and TRT was conducted at a tertiary Canadian academic cancer centre from 2016 to 2020. TRT was defined as any course of radiotherapy with lung parenchyma in the treated field. The primary endpoint was incidence and time to symptomatic pneumonitis. Variables predictive of time to pneumonitis were determined using multivariable Cox proportional hazards regression. Results: In total, 41 patients received osimertinib and TRT to 68 lesions. Five patients developed grade ≥ 2 pneumonitis (12.2%), of which one was grade 4 (2.4%) and one was grade 5 (2.4%). Median time to any-grade pneumonitis was 56 days. Among the 41 patients, TRT preceded osimertinib in 13, osimertinib was confirmed to be held during TRT in 12, confirmed to overlap TRT in 5, and status was undocumented in 11. Two of the five symptomatic cases occurred after re-irradiation, and four occurred after treatment of centrally located lesions. Exploratory multivariable analyses were highly uncertain given the five grade ≥ 2 events; the association with confirmed osimertinib overlap had a wide confidence interval (HR 3.36, 95% CI 0.13–86.56). Concluoksion: Symptomatic pneumonitis occurred in 12.2% of this selected cohort, including rare severe and fatal events. Findings are hypothesis generating and do not establish the safety or harm of overlapping osimertinib with TRT.