Auster ME, Xu Q, Kowalski J and Kaur S*
Introduction: Molecular testing has become standard of care in the treatment of Non-Small Cell Lung Cancer (NSCLC). Active driver mutations will often guide therapies, especially in the advanced setting, in which resistance is a likely event. With increasing molecular testing results, it is unclear how to effectively prioritize them to structure each next line of treatment. Herein, we report on a case with a MET exon 14 skipping mutation who developed resistance after treatment with a type 1b targeted TKI.
Case report: Our patient presented as a 76-year-old Hispanic female with newly diagnosed stage IV NSCLC adenocarcinoma. She was found to have a MET exon 14 skipping mutation and was initiated on capmatenib in accordance with the geometry trial. She had a partial response with resolution of her symptoms for about 6 months post therapy initiation and subsequently progressed. Molecular testing showed a MET D1228N resistance and a CCDC6 RET fusion mutation, along with numerous Variants of Unknown Significance (VUS). She was switched to selpercatinib and progressed after a month on treatment. An analysis of variants combined with a high CPS score indicated immunotherapy treatment that the patient has since started.
Conclusion: After treatment with targeted therapies, resistance mechanisms are found with increasing frequency. Herein, we present a patient who developed a classic MET D1228N resistance mechanism and RET fusion, bypassing resistance mechanism. An analysis of molecular variants provided novel insight into the VUS, RBM10, to support immunotherapy. This case demonstrates the need to look for actionable information beyond key findings to determine next therapeutic steps.