Ramucirumab and erlotinib combination as first-line treatment for advanced or recurrent non-small cell lung cancer harboring EGFR Exon21 L858R mutation: a multicenter retrospective observational cohort study in Japan (REAL-SPEED).
{"title":"Ramucirumab and erlotinib combination as first-line treatment for advanced or recurrent non-small cell lung cancer harboring <i>EGFR</i> Exon21 L858R mutation: a multicenter retrospective observational cohort study in Japan (REAL-SPEED).","authors":"Masashi Ishihara, Takahisa Kawamura, Yukiko Namba, Yuki Takeyasu, Yukihiro Hasegawa, Yuki Sato, Yoshiki Negi, Tomohiro Oba, Toshiyuki Sumi, Hirokuni Hirata, Hidemitsu Funabashi, Yuko Oya, Hajime Kikuchi, Naoko Katsurada, Takeshi Nakatani, Keiko Tanimura, Taku Nakagawa, Naoya Takeda, Takahiro Asami, Osamu Honjo, Hiromi Nagashima, Takumi Yamaura, Norihiko Hata, Miyako Kitazono, Naoya Nishioka, Akihiro Tamiya, Yuichi Sakamori, Ryota Shigaki, Kyoichi Kaira, Ryoichi Honda, Takashi Matsui, Eriko Suzuki, Kentaro Ito, Kojiro Otsuka, Naoto Takase, Yusuke Murakami, Kazuhiko Matsuno, Sumito Inoue, Akira Kisohara, Sojiro Kusumoto, Hiroe Aoshima, Yumiko Kakizaki, Akihito Kubo, Akito Hata, Nobuhisa Ishikawa, Kosuke Hamai, Nobuhiro Kanaji, Toshihiro Misumi, Noriyuki Matsutani, Nobuhiko Seki","doi":"10.1177/17588359251344010","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong><i>EGFR</i> L858R mutation is associated with poorer efficacy of EGFR-tyrosine kinase inhibitors (TKIs) than <i>EGFR</i> 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.</p><p><strong>Objectives: </strong>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.</p><p><strong>Design: </strong>A multicenter, noninterventional, retrospective cohort study.</p><p><strong>Methods and analysis: </strong>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.</p><p><strong>Discussion: </strong>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.</p><p><strong>Trial registration: </strong>UMIN Clinical Trials Registry identifier: UMIN000052047.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251344010"},"PeriodicalIF":4.2000,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174667/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic Advances in Medical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17588359251344010","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: EGFR L858R mutation is associated with poorer efficacy of EGFR-tyrosine kinase inhibitors (TKIs) than EGFR 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.
Objectives: 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.
Design: A multicenter, noninterventional, retrospective cohort study.
Methods and analysis: 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.
Discussion: 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.
期刊介绍：
Therapeutic Advances in Medical Oncology is an open access, peer-reviewed journal delivering the highest quality articles, reviews, and scholarly comment on pioneering efforts and innovative studies in the medical treatment of cancer. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in medical oncology, providing a forum in print and online for publishing the highest quality articles in this area. This journal is a member of the Committee on Publication Ethics (COPE).
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