Osimertinib-Induced Lung Injury and Treatment Rechallenge: Clinical Insights From a Case Report With a Comprehensive Literature Review

作者：Fabrizio Citarella, Emanuele Claudio Mingo, M. Fiorenti, Marco Russano, Giuseppe Perrone, Giulia La Cava, Valentina Santo, Alessia Vendittelli, Leonardo Brunetti, Cecilia Saracino, Ludovica Esposito, Andrea Malgeri, Sara Ramella, B. Vincenzi, G. Tonini, Alessio Cortellini · 发表于：Clinical Lung Cancer · 年份：2025 · DOI：10.1016/j.cllc.2025.12.006 · 研究领域：Lung Cancer Treatments and Mutations、Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Chronic Myeloid Leukemia Treatments

Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) widely used in EGFR mutant non-small cell lung cancer (NSCLC). Despite a favorable safety profile, osimertinib-induced lung injury (OILI) remains a rare but clinically significant adverse event. Guidelines recommend permanent discontinuation after severe cases; the rechallenge feasibility in selected patients remains an area of ongoing debate. We report a case of a 70-year-old patient with EGFR mutant NSCLC who developed grade 4 OILI requiring hospitalization. After resolution with corticosteroids, treatment was switched to afatinib. The patient later progressed showing a de novo EGFR T790M mutation and MET amplification. Considering the limited treatment options, a carefully monitored osimertinib rechallenge at a reduced dose (40 mg/d) was attempted. The patient tolerated treatment without pneumonitis recurrence and achieved disease control for several months before ultimately progressing. To contextualize this case, we conducted a scoping review of the available literature on osimertinib administration after lung toxicity. Among 27 studies comprising 1645 patients, 449 (27.3%) developed OILI. One hundred eighty nine (42%) were re-treated, either with (114) or without (75) a temporary interruption. The reported risk of recurrence after rechallenge was low, particularly in cases of mild-to-moderate lung injury. In more severe cases the risk was difficult to determine base...