• Yuki Sato, Hiromitsu Sumikawa, Ryota Shibaki, Takeshi Morimoto, Yoshihiko Sakata, Yuko Oya, Motohiro Tamiya, Hidekazu Suzuki, Hirotaka Matsumoto, Takashi Yokoi, Kazuki Hashimoto, Hiroshi Kobe, Aoi Hino, Megumi Inaba, Yoko Tsukita, Hideki Ikeda, Daisuke Arai, Hirotaka Maruyama, Satoshi Hara, Shinsuke Tsumura, Shinya Sakata, and Daichi Fujimoto.
• Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan. Electronic address: yuki1130sato@gmail.com.
• Chest. 2022 Nov 1; 162 (5): 118811981188-1198.

BackgroundOsimertinib has demonstrated impressive efficacy as a first-line treatment for patients with advanced epidermal growth factor receptor (EGFR) mutation-positive (m+) lung cancer. Drug-related pneumonitis (DRP) is a potentially lethal complication of osimertinib treatment, but reliable real-world data currently are lacking.Research QuestionWhat is the prevalence of osimertinib-induced DRP in first-line settings? What are the characteristics, clinical impact, and risk factors of osimertinib-induced DRP?Study Design And MethodsWe conducted a retrospective multicenter cohort study of patients who received osimertinib as a first-line treatment for advanced EGFR m+ non-small cell lung cancer (NSCLC) between August 2018 and December 2019. All chest CT scans and clinical information during osimertinib exposure were collected until June 2020. The primary end point was DRP incidence identified through central review.ResultsA total of 452 patients from 18 institutions were evaluated. Eighty patients (18%) had a diagnosis of DRP (all grades), and 21 patients (4.6%) had a diagnosis of grade 3 or more DRP. Among the patients with DRP, 46% were identified as having transient asymptomatic pulmonary opacity (TAPO). Regarding the CT scan patterns, organizing pneumonia, simple pulmonary eosinophilia, hypersensitivity pneumonia, diffuse alveolar damage, and nonspecific interstitial pneumonia were found in 30, 21, 18, 9, and two patients (38%, 26%, 23%, 11%, and 3%), respectively. In multivariate analysis, smoking history was identified as an independent risk factor for DRP (hazard ratio, 1.72; 95% CI, 1.01-2.89; P = .046). In the 3-month landmark analysis, DRP was associated with poor treatment efficacy; however, the presence of TAPO did not affect treatment efficacy negatively.InterpretationFor osimertinib treatment in first-line settings, the frequency of DRP was considerably elevated to 18 %, and half of these patients exhibited TAPO features.Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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