Selpercatinib and capmatinib combination promotes sustained complete response in novel ISOC1-RET fusion lung cancer after resistance to RET inhibitor via MET amplification: Case Report

RET fusions occur in 1–2% of non-small cell lung cancer. Selpercatinib and pralsetinib are selective RET inhibitors with significant improvement of outcome in patients with tumor harboring RET fusion; however, resistance mechanisms appear frequently, mainly driven by MAPK pathway bypass, secondary R...

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Bibliographic Details
Published in:Frontiers in Oncology
Main Authors: Caio Abner Leite, Raíssa Pierri Carvalho, Felipe Marques da Costa, Augusto Kreling Medeiros, Fabio Augusto Schutz, William Nassib William
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-10-01
Subjects:
lung adenocarcinoma
RET fusion
MET amplification
selpercatinib
capmatinib
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2023.1264231/full
Description
Summary:RET fusions occur in 1–2% of non-small cell lung cancer. Selpercatinib and pralsetinib are selective RET inhibitors with significant improvement of outcome in patients with tumor harboring RET fusion; however, resistance mechanisms appear frequently, mainly driven by MAPK pathway bypass, secondary RET mutations, or in 5% via MET amplification. Co-inhibition of RET and MET is a compelling strategy for overcoming MET-dependent resistance to RET inhibitors and potentially other inhibitors. To our knowledge, this is the first report of a novel ISOC1-RET fusion lung cancer with a durable complete response to selpercatinib, with resistance via MET amplification, which was overcome by the successful combination of selpercatinib and capmatinib.
ISSN:2234-943X

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