表皮生长因子受体（EGFR）突变阳性晚期非小细胞肺癌一线使用奥希替尼的全貌：真实世界的疗效、安全性、进展模式及治疗后治疗（令和研究）
The Whole Picture of First-Line Osimertinib for EGFR Mutation-Positive Advanced NSCLC: Real-World Efficacy, Safety, Progression Pattern, and Posttreatment Therapy (Reiwa Study).
作者信息
Watanabe Kageaki, Hosomi Yukio, Naoki Katsuhiko, Nakahara Yoshiro, Tsukita Yoko, Matsumoto Hirotaka, Yoh Kiyotaka, Fujisaka Yasuhito, Takahashi Satoshi, Takata Saori, Usui Kazuhiro, Kishi Kazuma, Naka Go, Tamano Shu, Uemura Kohei, Kunitoh Hideo
机构信息
Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
Department of Respiratory Medicine, Kitasato University School of Medicine, Kanagawa, Japan.
出版信息
JTO Clin Res Rep. 2024 Sep 7;5(11):100720. doi: 10.1016/j.jtocrr.2024.100720. eCollection 2024 Nov.
INTRODUCTION
Osimertinib is used as the first-line treatment for EGFR mutation-positive NSCLC. Nevertheless, its efficacy and safety in clinical practice remain to be fully elucidated and the pattern of progression and the optimal subsequent treatment after osimertinib remains unclear.
METHODS
This was a multicenter prospective observational study. EGFR mutation-positive patients with NSCLC who started first-line osimertinib from September 2018 to August 2020 were enrolled and followed up until August 2022.
RESULTS
A total of 583 patients received osimertinib. The median progression-free and overall survival were 20.0 (95% confidence interval [CI]: 17.6-21.7) months and 41.0 (95% CI: 37.1-44.1) months, respectively. Grade 3 or worse adverse events were observed in 136 patients (23.3%). Progression patterns were categorized as central nervous system only, oligo-progression, and multiple organs on the basis of the Response Evaluation Criteria in Solid Tumors-progressive disease and occurred in 37 (10.8%), 156 (45.4%), and 151 patients (43.9%). The patient's condition on progression was asymptomatic in 195 patients (56.7%). Osimertinib was continued in 163 patients (47.4%) after confirming progression. In clinically stable population with progressive disease (n = 247), survival after progression was 13.3 (95% CI: 10.9-16.4) months for those who continued osimertinib beyond progressive disease (n = 124), and 24.1 (95% CI: 17.7-34.0) months for those who discontinued osimertinib (n = 123) (hazard ratio = 2.01, 95% CI: 1.38-2.91, = 0.0002). Platinum plus pemetrexed had the best overall survival benefits after osimertinib.
CONCLUSIONS
First-line osimertinib was found to have good effectiveness comparable to that reported in pivotal studies. Nevertheless, osimertinib should be discontinued among those who develop progression.
TRIAL REGISTRATION NUMBER
UMIN000038683.
引言
奥希替尼被用作表皮生长因子受体（EGFR）突变阳性的非小细胞肺癌（NSCLC）的一线治疗药物。然而，其在临床实践中的疗效和安全性仍有待充分阐明，奥希替尼治疗后的疾病进展模式及最佳后续治疗方案仍不明确。
方法
这是一项多中心前瞻性观察性研究。纳入2018年9月至2020年8月开始一线使用奥希替尼治疗的EGFR突变阳性NSCLC患者，并随访至2022年8月。
结果
共有583例患者接受了奥希替尼治疗。无进展生存期和总生存期的中位数分别为20.0个月（95%置信区间[CI]：17.6 - 21.7）和41.0个月（95% CI：37.1 - 44.1）。136例患者（23.3%）发生了3级或更严重的不良事件。根据实体瘤疗效评价标准中的疾病进展情况，将进展模式分为仅中枢神经系统进展、寡进展和多器官进展，分别有37例（10.8%）、156例（45.4%）和151例患者（43.9%）。195例患者（56.7%）在疾病进展时无症状。确认疾病进展后，163例患者（47.4%）继续使用奥希替尼。在疾病进展但临床稳定的人群（n = 247）中，疾病进展后继续使用奥希替尼的患者（n = 124）的生存期为13.3个月（95% CI：10.9 - 16.4），而停用奥希替尼的患者（n = 123）的生存期为24.1个月（95% CI：17.7 - 34.0）（风险比 = 2.01，95% CI：1.38 - 2.91，P = 0.0002）。奥希替尼治疗后，铂类联合培美曲塞具有最佳的总生存获益。
结论
发现一线使用奥希替尼具有良好的疗效，与关键研究中报道的疗效相当。然而，疾病进展的患者应停用奥希替尼。
试验注册号
UMIN000038683。
Zotero 插件