AUTHOR=Leite Caio Abner , Carvalho Raíssa Pierri , da Costa Felipe Marques , Medeiros Augusto Kreling , Schutz Fabio Augusto , William William Nassib 

TITLE=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

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1264231

DOI=10.3389/fonc.2023.1264231

ISSN=2234-943X

ABSTRACT=<p><italic>RET</italic> fusions occur in 1–2% of non-small cell lung cancer. Selpercatinib and pralsetinib are selective <italic>RET</italic> inhibitors with significant improvement of outcome in patients with tumor harboring <italic>RET</italic> fusion; however, resistance mechanisms appear frequently, mainly driven by MAPK pathway bypass, secondary <italic>RET</italic> mutations, or in 5% via <italic>MET</italic> amplification. Co-inhibition of <italic>RET</italic> and <italic>MET</italic> is a compelling strategy for overcoming <italic>MET</italic>-dependent resistance to <italic>RET</italic> inhibitors and potentially other inhibitors. To our knowledge, this is the first report of a novel <italic>ISOC1-RET</italic> fusion lung cancer with a durable complete response to selpercatinib, with resistance via <italic>MET</italic> amplification, which was overcome by the successful combination of selpercatinib and capmatinib.</p>