Hirata Tsuyoshi, 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, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan.
Department of Thoracic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
Jpn J Clin Oncol. 2025 Mar 5;55(3):269-274. doi: 10.1093/jjco/hyae176.
Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is a first-line therapy for advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR mutations, including both sensitizing and T790M resistance mutations. Its real-world efficacy against uncommon EGFR mutations remains under-researched.
The REIWA study, a multicentric, prospective, observational study conducted in Japan from September 2018 to August 2020, enrolled patients with advanced or recurrent EGFR mutation-positive NSCLC receiving osimertinib. Data on clinical outcomes, safety, disease progression, and subsequent treatments were collected for patients with uncommon EGFR mutations.
Of 583 patients receiving osimertinib, 39 (6.7%) had an uncommon EGFR mutation. The present study included 32 of these patients after excluding seven patients with an exon 20 insertion mutation. The overall objective response rate was 53.1% [95% confidence interval (CI): 36.4-69.1], and the disease control rate was 78.1% (95% CI: 61.0-89.3). The median progression-free survival was 9.4 months (95% CI: 5.0-20.0), and the median overall survival (OS) was 21.8 (95% CI: 14.4-NA) months. Notably, patients with an exon21 L861Q mutation had a significantly longer OS than those with an exon18 G719X mutation, the respective values being 37.8 and 9.7 months (hazard ratio: 0.29; 95% CI: 0.10-0.85; P = 0.02). The rate of grade 3 or worse adverse events was 10.3%. Seven out of 32 (21.9%) patients showed progression involving only the central nervous system.
Osimertinib demonstrated efficacy and tolerability in the clinical setting in patients with uncommon EGFR mutation-positive NSCLC.
奥希替尼是第三代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂，是具有EGFR突变（包括敏感性和T790M耐药突变）的晚期或转移性非小细胞肺癌（NSCLC）的一线治疗药物。其针对罕见EGFR突变的实际疗效仍研究不足。
REIWA研究是一项于2018年9月至2020年8月在日本进行的多中心、前瞻性观察性研究，纳入接受奥希替尼治疗的晚期或复发性EGFR突变阳性NSCLC患者。收集了罕见EGFR突变患者的临床结局、安全性、疾病进展及后续治疗的数据。
在583例接受奥希替尼治疗的患者中，39例（6.7%）有罕见EGFR突变。在排除7例有外显子20插入突变的患者后，本研究纳入了其中32例患者。总体客观缓解率为53.1%[95%置信区间（CI）：36.4 - 69.1]，疾病控制率为78.1%（95%CI：61.0 - 89.3）。中位无进展生存期为9.4个月（95%CI：5.0 - 20.0），中位总生存期（OS）为21.8（95%CI：14.4 - NA）个月。值得注意的是，外显子21 L861Q突变患者的OS显著长于外显子18 G719X突变患者，分别为37.8个月和9.7个月（风险比：0.29；95%CI：0.10 - 0.85；P = 0.02）。3级或更严重不良事件的发生率为10.3%。32例患者中有7例（21.9%）仅出现中枢神经系统进展。
奥希替尼在罕见EGFR突变阳性NSCLC患者的临床治疗中显示出疗效和耐受性。
