Impact of pre-existing interstitial lung abnormal shadow on lung injury development and severity in patients of non-small cell lung cancer treated with osimertinib

Background First-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) sometimes causes lung injury, thereby affecting survival. Although pre-existing interstitial lung abnormal shadow (pre-ILS) increases the risk of lung injury by EGFR-TKIs, its impact on osimertinib, a third-generation EGFR-TKI, remains unknown. Patients and Methods This retrospective cohort study consecutively enrolled patients of EGFR-mutated non-small cell lung cancer treated with osimertinib. Computed tomography images were obtained and evaluated independently by three pulmonologists in a blinded manner. Factors associated with lung injury were assessed using a logistic regression model. Survival curves were calculated by the Kaplan-Meier method and compared using a log-rank test. Results Of the 195 patients, 40 had pre-ILS, and 21 (8 with and 13 without pre-ILS) developed lung injury during the observation period. Multivariate analysis revealed that pre-ILS was independently associated with lung injury (odds ratio, 3.1; 95% confidence interval [CI], 1.1-8.2; p = 0.025). Severe (>= Grade 3) lung injury was observed in eight (4.1%) patients, of whom, two (5%) and six (3.9%) had and did not have pre-ILS (p = 0.67), respectively. Grade 5 lung injury was not observed, and survival curves were similar between the patients who developed lung injury and those who did not (median 11 vs. 12 months; hazard ratio, 1.2; 95% CI, 0.56-2.7; p = 0.60). Conclusions Pre-ILS increased the risk of lung injury in patients of non-small cell lung cancer treated with osimertinib, while the severity of lung injury was not clearly affected by the presence of pre-ILS.