Department of Respiratory Medicine, Shonan Fujisawa Tokushukai Hospital, 1-5-1 Tsujido Kandai, Fujisawa, Kanagawa, 251-0041, Japan.
Department of Medical Oncology and Hematology, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki, Chuo, Kobe, Hyogo, 650-0017, Japan.
Target Oncol. 2024 Nov;19(6):925-939. doi: 10.1007/s11523-024-01094-5. Epub 2024 Sep 20.
Osimertinib shows higher effectiveness than first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in the initial treatment of EGFR-mutated non-small cell lung cancer. However, its superiority in terms of overall survival in the Asian population, especially Japanese patients, remains uncertain.
To evaluate the survival benefit of osimertinib over other EGFR-TKIs in Japanese patients, using real-world data. METHODS : As part of the Tokushukai REAl-world Data project, a retrospective multi-institutional study across 46 hospitals in Japan was conducted to evaluate the overall survival of patients with advanced EGFR-mutated non-small cell lung cancer using propensity score matching. The study involved patients receiving osimertinib as the first-line treatment (1L-Osi), those initially treated with other EGFR-TKIs (1L-non-Osi), and those receiving osimertinib after initial EGFR-TKI treatment (2L/later-Osi) between April 2010 and December 2022 and followed up until April 2023.
Among 1062 Japanese patients with EGFR-mutated non-small cell lung cancer, 416 (39.2%) received 1L-Osi, while 646 (60.8%) received 1L-non-Osi, including 139 (13.1%) who received 2L/later-Osi. Within these groups, 416 (39.2%), 293 (27.6%), and 75 (7.1%) patients received first-line EGFR-TKI treatment post-osimertinib approval as a later-line treatment in Japan (March 2016). After propensity score matching, the overall survival of the 1L-Osi group was comparable to that of the 1L-non-Osi group in the post-March 2016 subset (n = 283, 42.0 vs 42.4 months). Similar trends were observed in the Del19 and L858R subgroups. The median overall survival of the 2L/later-Osi group was notably long: 60.2 months post-March 2016 (n = 75). A subgroup analysis based on initial EGFR-TKI treatment in the 1L-non-Osi and 2L/later-Osi groups revealed no significant differences among the gefitinib, erlotinib, and afatinib groups.
Based on real-world data, osimertinib did not show a significant improvement in overall survival compared to other EGFR-TKIs as a first-line treatment for EGFR-mutated advanced non-small cell lung cancer in the Japanese (Asian) population.
This study was registered at the University Hospital Medical Information Network Clinical Trials Registry on 9 March, 2023 (identification UMIN000050552).
奥希替尼在 EGFR 突变型非小细胞肺癌的初始治疗中比第一代表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂（TKI）具有更高的疗效。然而，其在亚洲人群，尤其是日本患者中的总生存优势仍不确定。
使用真实世界数据评估奥希替尼在日本患者中的生存获益。
作为 Tokushukai REAl-world Data 项目的一部分，在日本的 46 家医院进行了一项回顾性多机构研究，通过倾向评分匹配评估接受奥希替尼（1L-Osi）作为一线治疗、初始接受其他 EGFR-TKI（1L-non-Osi）治疗以及初始 EGFR-TKI 治疗后接受奥希替尼（2L/later-Osi）的晚期 EGFR 突变型非小细胞肺癌患者的总生存期。研究纳入了 2010 年 4 月至 2022 年 12 月期间接受治疗并随访至 2023 年 4 月的患者。
在 1062 例日本 EGFR 突变型非小细胞肺癌患者中，416 例（39.2%）接受 1L-Osi 治疗，646 例（60.8%）接受 1L-non-Osi 治疗，其中 139 例（13.1%）接受 2L/later-Osi 治疗。在这些组中，416 例（39.2%）、293 例（27.6%）和 75 例（7.1%）患者在奥希替尼获得批准后作为后续线治疗在日本接受了一线 EGFR-TKI 治疗（2016 年 3 月）。在倾向评分匹配后，1L-Osi 组在 2016 年 3 月后亚组（n=283，42.0 个月 vs. 42.4 个月）的总生存期与 1L-non-Osi 组相当。在 Del19 和 L858R 亚组中也观察到类似的趋势。2L/later-Osi 组的中位总生存期明显较长：2016 年 3 月后 60.2 个月（n=75）。在 1L-non-Osi 和 2L/later-Osi 组中根据初始 EGFR-TKI 治疗进行的亚组分析显示，吉非替尼、厄洛替尼和阿法替尼组之间没有显著差异。
基于真实世界数据，奥希替尼作为 EGFR 突变型晚期非小细胞肺癌的一线治疗，与其他 EGFR-TKI 相比，在日本（亚洲）人群中并未显示出总生存期的显著改善。
本研究于 2023 年 3 月 9 日在大学医院医学信息网络临床试验注册中心注册（识别号 UMIN000050552）。
