A novel gene fusion variant in lung adenocarcinoma with prolonged response to tepotinib: a case report.

BACKGROUND

rearrangements are infrequently observed in non-small cell lung cancer (NSCLC). Advanced genomic detection techniques have unveiled such infrequent genomic variations, particularly fusions in approximately 0.5% of NSCLC patients. Tyrosine kinase inhibitors (TKIs) have revolutionized the standard of care in lung cancer and more recently a second generation MET TKI tepotinib received Food and Drug Administration (FDA) approval for MET exon 14 alterations in metastatic NSCLC. Despite this, the therapeutic landscape for -rearranged NSCLC patients remains significantly unexplored. The aim of our report is to detail a unique case of a patient with metastatic lung adenocarcinoma with a novel fusion detected by next-generation sequencing (NGS) following previous treatment resistance.

CASE DESCRIPTION

A 73-year-old female was initially started on carboplatin, pemetrexed and pembrolizumab with maintenance, but eventually had progression in the left upper lobe (LUL). Upon progression she was enrolled in a clinical trial of a monoclonal antibody with or without a PD-1 inhibitor, but brain metastasis progression was eventually detected by magnetic resonance imaging (MRI) requiring stereotactic radiosurgery (SRS) and a craniotomy. The trial drug was eventually discontinued due to progression and toxicity and NGS on bronchoscopy tissue revealed fusion. The patient was initiated on tepotinib and continues with clinical and radiological stable disease for over 12 months. The patient's response to a MET inhibitor, tepotinib, underscores the potential efficacy of selective MET inhibitors for individuals with previously unexplored fusions.

CONCLUSIONS

The positive response to tepotinib of a patient with NSCLC harboring a novel -Fusion underscores the importance of the use of comprehensive next-generational sequencing-based panels and highlights the necessity for additional research and clinical exploration of selective MET inhibitors for managing NSCLC with rearrangements.