Repotrectinib Overcomes F2004V Resistance Mutation in ROS1-Rearranged NSCLC: A Case Report

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports Pub Date : 2023-11-01 DOI:10.1016/j.jtocrr.2023.100555

Elio Gregory Pizzutilo MD , Alberto Giuseppe Agostara MD , Laura Roazzi MD , Rebecca Romanò MD , Valentina Motta PhD , Calogero Lauricella PhD , Giovanna Marrapese PhD , Giulio Cerea MD , Diego Signorelli MD, PhD , Silvio Marco Veronese PhD , Laura Giuseppina Giannetta MD , Andrea Sartore-Bianchi MD , Salvatore Siena MD

{"title":"Repotrectinib Overcomes F2004V Resistance Mutation in ROS1-Rearranged NSCLC: A Case Report","authors":"Elio Gregory Pizzutilo MD , Alberto Giuseppe Agostara MD , Laura Roazzi MD , Rebecca Romanò MD , Valentina Motta PhD , Calogero Lauricella PhD , Giovanna Marrapese PhD , Giulio Cerea MD , Diego Signorelli MD, PhD , Silvio Marco Veronese PhD , Laura Giuseppina Giannetta MD , Andrea Sartore-Bianchi MD , Salvatore Siena MD","doi":"10.1016/j.jtocrr.2023.100555","DOIUrl":null,"url":null,"abstract":"<div><p>ROS1 tyrosine kinase inhibitors (TKIs) were found to provide a substantial clinical benefit for patients with advanced ROS1-positive (ROS1+) NSCLC. Nevertheless, TKI resistance inevitably develops with different mechanisms, preventing prolonged responses. For this reason, next-generation compounds are under clinical development. ROS1 F2004 substitutions have been previously detected on circulating tumor DNA of patients progressing to entrectinib. Hereby, we report the case of a patient with ROS1+ NSCLC in which F2004V-acquired mutation was detected on a site of disease progression, after entrectinib and crizotinib failure. A subsequent treatment with next-generation TKI repotrectinib led to disease response, providing the first clinical evidence of activity of repotrectinib against F2004V resistance mutation.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":null,"pages":null},"PeriodicalIF":3.0000,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266636432300098X/pdfft?md5=cb2e257dc0f7c9a2548efebc9427216f&pid=1-s2.0-S266636432300098X-main.pdf","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JTO Clinical and Research Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S266636432300098X","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 1

Abstract

ROS1 tyrosine kinase inhibitors (TKIs) were found to provide a substantial clinical benefit for patients with advanced ROS1-positive (ROS1+) NSCLC. Nevertheless, TKI resistance inevitably develops with different mechanisms, preventing prolonged responses. For this reason, next-generation compounds are under clinical development. ROS1 F2004 substitutions have been previously detected on circulating tumor DNA of patients progressing to entrectinib. Hereby, we report the case of a patient with ROS1+ NSCLC in which F2004V-acquired mutation was detected on a site of disease progression, after entrectinib and crizotinib failure. A subsequent treatment with next-generation TKI repotrectinib led to disease response, providing the first clinical evidence of activity of repotrectinib against F2004V resistance mutation.

查看原文本刊更多论文

Repotractinib克服ROS1重排非小细胞肺癌癌症中F2004V耐药性突变的病例报告

ROS1酪氨酸激酶抑制剂(TKIs)被发现为晚期ROS1阳性(ROS1+) NSCLC患者提供了实质性的临床益处。然而，TKI耐药性不可避免地以不同的机制发展，防止长期反应。因此，新一代化合物正在进行临床开发。ROS1 F2004替代先前已在进展为肠替尼的患者的循环肿瘤DNA中检测到。在此，我们报告了一例ROS1+ NSCLC患者，在enterrectinib和crizotinib失效后，在疾病进展部位检测到f2004v获得性突变。随后使用下一代TKI repotrectinib治疗导致疾病缓解，提供了repotrectinib抗F2004V耐药突变活性的第一个临床证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊