Durable response to amivantamab in treatment refractory NSCLC harboring EGFR and complex MET mutations: A case report.

Targeted therapies have revolutionized treatment for metastatic non-small cell lung cancer (NSCLC) with oncogenic driver mutations. However, challenges arise in managing concurrent mutations and overcoming resistance. We present the case of a patient with epidermal growth factor receptor (EGFR) (L747_A750delinsP exon19 deletion) and mesenchymal-epithelial transition factor (MET) mutations (D1228H, D1228N, D1228Y, Y1230H, MET amplification) who achieved a durable response to amivantamab (14 months ongoing) after progression on multiple lines of therapy including platinum-based chemotherapy, EGFR tyrosine kinase inhibitors (TKI) and combination TKI and MET inhibitors. This case highlights the utility of longitudinal next-generation sequencing (NGS) testing to identify acquired resistance and the need for continued research into understanding mechanisms of resistance to help develop future treatment strategies.

Framework for Implementing and Tracking a Molecular Tumor Board at a National Cancer Institute-Designated Comprehensive Cancer Center.

BACKGROUND: Over the past few years, tumor next-generation sequencing (NGS) panels have evolved in complexity and have changed from selected gene panels with a handful of genes to larger panels with hundreds of genes, sometimes in combination with paired germline filtering and/or testing. With this move toward increasingly large NGS panels, we have rapidly outgrown the available literature supporting the utility of treatments targeting many reported gene alterations, making it challenging for oncology providers to interpret NGS results and make a therapy recommendation for their patients. METHODS: To support the oncologists at Vanderbilt-Ingram Cancer Center (VICC) in interpreting NGS reports for patient care, we initiated two molecular tumor boards (MTBs)-a VICC-specific institutional board for our patients and a global community MTB open to the larger oncology patient population. Core attendees include oncologists, hematologist, molecular pathologists, cancer geneticists, and cancer genetic counselors. Recommendations generated from MTB were documented in a formal report that was uploaded to our electronic health record system. RESULTS: As of December 2020, we have discussed over 170 patient cases from 77 unique oncology providers from VICC and its affiliate sites, and a total of 58 international patient cases by 25 unique providers from six different countries across the globe. Breast cancer and lung cancer were the most presented diagnoses. CONCLUSION: In this article, we share our learning from the MTB experience and document best practices at our institution. We aim to lay a framework that allows other institutions to recreate MTBs. IMPLICATIONS FOR PRACTICE: With the rapid pace of molecularly driven therapies entering the oncology care spectrum, there is a need to create resources that support timely and accurate interpretation of next-generation sequencing reports to guide treatment decision for patients. Molecular tumor boards (MTB) have been created as a response to this knowledge gap. This report shares implementation strategies and best practices from the Vanderbilt experience of creating an institutional MTB and a virtual global MTB for the larger oncology community. This report describe a reproducible framework that can be adopted to initiate MTBs at other institutions.