INTRODUCTION Using real-world Japanese post-marketing data, we characterized interstitial lung disease (ILD) development during second- or later-line osimertinib treatment for epidermal growth factor receptor-mutation-positive non-small cell lung cancer. Retrospective radiologic image evaluation of patients developing ILD was also performed. METHODS Patients who had ILD events reported as an adverse drug reaction by their physicians and were assessed as having developed ILD based on the judgement of an ILD expert committee in Japan were included. RESULTS Among 3578 patients, 252 ILD events were reported in 245 (6.8%) patients by the attending physicians. The median (range) time to first onset of ILD after osimertinib treatment initiation was 63.0 (5-410) days, and 29 patients with a fatal outcome were reported. The ILD expert committee assessed 231/3578 patients (6.5%) as having ILD. Prior nivolumab therapy (adjusted odds ratio: 2.84; 95% confidence interval: 1.98-4.07) and history/concurrence of ILD (3.51; 2.10-5.87) were identified as factors potentially associated with ILD onset during osimertinib treatment. In patients who had received prior nivolumab treatment, the number and proportion of patients developing ILD were highest for patients who discontinued nivolumab treatment within the first month before initiating osimertinib; trends for decreasing incidence and proportion were observed with increasing duration between the end of nivolumab treatment and the initiation of osimertinib treatment. CONCLUSIONS The frequency of ILD was consistent with the known osimertinib safety profile in the Japanese population. History/concurrence of ILD and history of prior nivolumab therapy are factors potentially associated with ILD onset during osimertinib treatment.

中文翻译：

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日本奥希替尼治疗表皮生长因子受体 T790M 阳性非小细胞肺癌患者间质性肺病发病率和影像学特征的真实世界评价

引言 使用真实世界的日本上市后数据，我们描述了在表皮生长因子受体突变阳性非小细胞肺癌二线或后线奥希替尼治疗期间间质性肺病 (ILD) 的发展。还对发生 ILD 的患者进行回顾性放射影像评估。方法 将发生 ILD 事件的患者报告为药物不良反应，并根据日本 ILD 专家委员会的判断评估为发生 ILD。结果 在 3578 名患者中，245 名（6.8%）患者的主治医师报告了 252 次 ILD 事件。奥希替尼治疗开始后到首次出现 ILD 的中位（范围）时间为 63.0 (5-410) 天，并报告了 29 名患者出现致命结果。ILD 专家委员会评估了 231/3578 名患者 (6.5%) 患有 ILD。既往纳武单抗治疗（调整比值比：2.84；95% 置信区间：1.98-4.07）和 ILD 病史/并发（3.51；2.10-5.87）被确定为可能与奥希替尼治疗期间 ILD 发病相关的因素。在既往接受过纳武单抗治疗的患者中，在开始奥希替尼之前的第一个月内停止纳武单抗治疗的患者发生 ILD 的人数和比例最高；随着纳武单抗治疗结束和奥希替尼治疗开始之间持续时间的增加，观察到发生率和比例下降的趋势。结论 ILD 的发生频率与日本人群中已知的奥希替尼安全性特征一致。