Ishihara Masashi, Kawamura Takahisa, Namba Yukiko, Takeyasu Yuki, Hasegawa Yukihiro, Sato Yuki, Negi Yoshiki, Oba Tomohiro, Sumi Toshiyuki, Hirata Hirokuni, Funabashi Hidemitsu, Oya Yuko, Kikuchi Hajime, Katsurada Naoko, Nakatani Takeshi, Tanimura Keiko, Nakagawa Taku, Takeda Naoya, Asami Takahiro, Honjo Osamu, Nagashima Hiromi, Yamaura Takumi, Hata Norihiko, Kitazono Miyako, Nishioka Naoya, Tamiya Akihiro, Sakamori Yuichi, Shigaki Ryota, Kaira Kyoichi, Honda Ryoichi, Matsui Takashi, Suzuki Eriko, Ito Kentaro, Otsuka Kojiro, Takase Naoto, Murakami Yusuke, Matsuno Kazuhiko, Inoue Sumito, Kisohara Akira, Kusumoto Sojiro, Aoshima Hiroe, Kakizaki Yumiko, Kubo Akihito, Hata Akito, Ishikawa Nobuhisa, Hamai Kosuke, Kanaji Nobuhiro, Misumi Toshihiro, Matsutani Noriyuki, Seki Nobuhiko
Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan.
Ther Adv Med Oncol. 2025 Jun 16;17:17588359251344010. doi: 10.1177/17588359251344010. eCollection 2025.
L858R mutation is associated with poorer efficacy of EGFR-tyrosine kinase inhibitors (TKIs) than Ex19del in patients with non-small cell lung cancer (NSCLC). However, ramucirumab (RAM) + erlotinib (ERL) therapy exhibited comparable efficacy between patients with L858R mutation and Ex19del mutation (median progression-free survival (PFS): 19.6 vs 19.4 months) in the RELAY study, with favorable PFS for both gene mutations at 19.4 months in the Japanese subset. Meanwhile, the FLAURA study revealed shorter PFS with osimertinib (OSI) for L858R mutation than Ex19del mutation, with poorer PFS in the Japanese subset than in the overall population. The treatment discontinuation rates of RAM + ERL and OSI in Japanese patients were 18% and 29%, respectively. Consequently, RAM + ERL may exhibit superior efficacy and safety in Japanese patients with the L858R mutation.
To evaluate the therapeutic efficacy and safety of RAM + ERL as a first-line treatment for advanced or recurrent NSCLC harboring the L858R mutation in Japanese patients.
A multicenter, noninterventional, retrospective cohort study.
This study will involve patients with advanced or recurrent NSCLC (ECOG PS score 0-2) with L858R mutation who received RAM + ERL between November 1, 2020 and August 31, 2023, with the planned sample size of 200 patients. The primary endpoint is time to treatment failure, and the secondary endpoints are overall survival, PFS, PFS2, time to discontinuation of any EGFR-TKI, time to failure of strategy, objective response rate, disease control rate, and safety. Exploratory endpoints are effects of ERL and RAM on PD-L1 expression and neutrophil-to-lymphocyte ratio.
To the best of our knowledge, this is the first retrospective study focusing on L858R mutations associated with the RELAY regimen, providing the corresponding real-world data.
UMIN Clinical Trials Registry identifier: UMIN000052047.
在非小细胞肺癌（NSCLC）患者中，L858R突变与表皮生长因子受体酪氨酸激酶抑制剂（TKIs）的疗效相比，比Ex19del突变患者更差。然而，在RELAY研究中，雷莫西尤单抗（RAM）联合厄洛替尼（ERL）治疗在L858R突变患者和Ex19del突变患者之间显示出相当的疗效（中位无进展生存期（PFS）：19.6个月对19.4个月），在日本亚组中，两种基因突变的PFS均为19.4个月，效果良好。同时，FLAURA研究显示，奥希替尼（OSI）治疗L858R突变患者的PFS比Ex19del突变患者短，日本亚组的PFS比总体人群更差。日本患者中RAM联合ERL和OSI的治疗中断率分别为18%和29%。因此，RAM联合ERL在日本L858R突变患者中可能表现出更好的疗效和安全性。
评估RAM联合ERL作为日本L858R突变的晚期或复发性NSCLC患者一线治疗的疗效和安全性。
一项多中心、非干预性、回顾性队列研究。
本研究将纳入2020年11月1日至2023年8月31日期间接受RAM联合ERL治疗的L858R突变的晚期或复发性NSCLC患者（东部肿瘤协作组体能状态评分0 - 2），计划样本量为200例患者。主要终点是治疗失败时间，次要终点是总生存期、PFS、PFS2、任何EGFR - TKI停药时间、治疗策略失败时间、客观缓解率、疾病控制率和安全性。探索性终点是ERL和RAM对PD - L1表达和中性粒细胞与淋巴细胞比值的影响。
据我们所知，这是第一项关注与RELAY方案相关的L858R突变的回顾性研究，提供了相应的真实世界数据。
UMIN临床试验注册标识符：UMIN000052047。
