Lorlatinib and capmatinib in a ROS1-rearranged NSCLC with MET-driven resistance: tumor response and evolution.

ABSTRACT: Acquired drug resistance remains a major problem across oncogene-addicted cancers. Elucidation of mechanisms of resistance can inform rational treatment strategies for patients relapsing on targeted therapies while offering insights into tumor evolution. Here, we report acquired MET amplification as a resistance driver in a ROS1-rearranged lung adenocarcinoma after sequential treatment with ROS1 inhibitors. Subsequent combination therapy with lorlatinib plus capmatinib, a MET-selective inhibitor, induced intracranial and extracranial tumor response. At relapse, sequencing of the resistant tumor revealed a MET D1246N mutation and loss of MET amplification. We performed integrated molecular analyses of serial tumor and plasma samples, unveiling dynamic alterations in the ROS1 fusion driver a

SUBMITTER: Schneider JL 

PROVIDER: S-EPMC10624912 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature