Kobayashi Takayuki, Watanabe Kageaki, Hosomi Yukio, Yoh Kiyotaka, Usui Kazuhiro, Kishi Kazuma, Naka Go, Tamano Shu, Uemura Kohei, Kunitoh Hideo
Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
Department of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan.
Jpn J Clin Oncol. 2025 Mar 5;55(3):275-282. doi: 10.1093/jjco/hyae178.
Osimertinib-induced interstitial lung disease in untreated EGFR-mutated, advanced non-small cell lung cancer is being reported at a higher rate in Japan than elsewhere. However, data on the interstitial lung disease incidence during first-line osimertinib therapy and the course of lung cancer treatments administered after interstitial lung disease onset in the real-world setting are scarce.
The present study reviewed the data from the Reiwa study, a multicentric, observational study examining the efficacy and safety of first-line osimertinib therapy in the clinical setting. Patients with EGFR-mutated non-small cell lung cancer who began osimertinib therapy between September 2018 and August 2020 were enrolled and followed until August 2022.
Among 583 patients receiving first-line osimertinib therapy, 75 (12.8%) had interstitial lung disease development, and 18 (3.0%) had at least grade 3 interstitial lung disease. Fifty-nine patients (78%) received some form of treatment following interstitial lung disease onset. An epidermal growth factor receptor-tyrosine kinase inhibitor rechallenge was performed in 31 patients (41%), with 18 (24%) receiving osimertinib again. Interstitial lung disease recurred in five (28%) of these 18 patients, none of 13 patients receiving another type of tyrosine kinase inhibitor, and seven (25%) of 28 patients receiving chemotherapy and/or immune checkpoint inhibitor therapy. The median overall survival after the initial osimertinib therapy was 38.4 months and 12.2 months for patients with interstitial lung disease grade 1-2 and grade 3-4, respectively (hazard ratio: 0.37; 95% confidence interval: 0.20-0.70; P = 0.002).
Patients with interstitial lung disease grade 3-4 had poorer survival during the first-line osimertinib therapy. A substantial risk of interstitial lung disease recurrence was associated with post-osimertinib therapy. Trial registration code: UMIN000038683.
在日本，未经治疗的表皮生长因子受体（EGFR）突变的晚期非小细胞肺癌患者中，奥希替尼诱发的间质性肺病报告率高于其他地区。然而，关于一线奥希替尼治疗期间间质性肺病的发病率以及在现实环境中间质性肺病发病后所进行的肺癌治疗过程的数据却很稀少。
本研究回顾了令和研究的数据，这是一项多中心观察性研究，旨在考察临床环境中一线奥希替尼治疗的疗效和安全性。纳入了2018年9月至2020年8月期间开始接受奥希替尼治疗的EGFR突变非小细胞肺癌患者，并随访至2022年8月。
在接受一线奥希替尼治疗的583例患者中，75例（12.8%）发生了间质性肺病，18例（3.0%）患有至少3级间质性肺病。59例患者（78%）在间质性肺病发病后接受了某种形式的治疗。31例患者（41%）进行了表皮生长因子受体酪氨酸激酶抑制剂再激发治疗，其中18例（24%）再次接受奥希替尼治疗。这18例患者中有5例（28%）间质性肺病复发，接受另一种酪氨酸激酶抑制剂治疗的13例患者中无一例复发，接受化疗和/或免疫检查点抑制剂治疗的28例患者中有7例（25%）复发。初始奥希替尼治疗后的中位总生存期，1-2级间质性肺病患者为38.4个月，3-4级间质性肺病患者为12.2个月（风险比：0.37；95%置信区间：0.20-0.70；P = 0.002）。
3-4级间质性肺病患者在一线奥希替尼治疗期间生存期较差。奥希替尼治疗后存在间质性肺病复发的重大风险。试验注册号：UMIN000038683。
