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

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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.

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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。

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