Cabozantinib Response in a Patient With NSCLC Harboring Both MET Exon 14 Skipping Mutation and Secondary RET Fusion: A Case Report

• DOI: 10.1016/j.jtocrr.2024.100647
• Publication Date: 2024-02-07T02:14:37Z
• Authors: Carlos Torrado; Jamie Feng; Elizabeth Faour; Natasha B. Leighl
• Keywords: Cabozantinib; Exon skipping; Targeted Therapy

MET exon 14 skipping mutation has emerged as a new oncogenic driver in NSCLC with available targeted therapies, including Food and Drug Administration–approved inhibitors capmatinib and tepotinib. Potential resistance mechanisms are beginning to be described and include several on-target and off-target mutations. Here, we report an emergent secondary RET fusion in a patient with a primary MET exon 14 skipping mutation that progressed on capmatinib after the initial response. Subsequently, this patient received both a RET inhibitor (selpercatinib) followed by another MET-targeted treatment (tepotinib) without clinical benefit. Thereafter, cabozantinib, a multikinase inhibitor with activity against RET and MET was started with a rapid clinical and radiologic benefit.