TARGETING MET: BREAKTHROUGH OF TEPOTINIB IN NSCLC THERAPY

Dr. Yuvraj Kaushal* and Dr. Pranav Goyal

Objective: The purpose of the presented article is to discuss the clinical implication of tepotinib, for NSCLC patients with MET exon 14 skipping mutations. Furthermore, the article covers topics such as the development of tepotinib, how this drug works, interactions of the drug with others, and the current state of the research on the drug. Methodology: We surveyed Science Direct, PubMed, Google Scholar, the USFDA, and the abstracts from the 2023 ASCO conference. Keywords “Tepotinib” and “VISION” and materials till February 2024 were used. We found 146 documents related to our research question and narrowed it to 106, ultimately including 41 articles in our study. Result: Lung cancer is the leading cause of cancer-related deaths worldwide, with significant contributions from genetic mutations such as EGFR, RET, KRAS, ALK, ROS1, BRAF, and MET. MET exon 14 (METex14) mutations and gene amplifications are particularly relevant in NSCLC. Tepotinib, a novel selective MET tyrosine kinase inhibitor, has shown clinical success in treating MET-driven tumors. The FDA granted tepotinib breakthrough therapy designation for NSCLC with METex14 skipping alterations. The phase II VISION trial demonstrated an objective response rate (ORR) of 46.5% and significant improvements in progression-free survival (PFS) and overall survival (OS). Its efficacy is enhanced by its ability to cross the blood-brain barrier, making it effective for brain metastases. Compared to other MET inhibitors like capmatinib, savolitinib, and crizotinib, it has shown superior results in certain metrics such as ORR and PFS. Adverse effects are generally mild to moderate, with edema being the most common making its profile safe with minimal withdrawals. Conclusion: Tepotinib marks an improvement in MET-directed therapy for the NSCLC patient population with METex14 skipping mutations due to the drugs’ impressive therapeutic effectiveness and reasonable safety profiles. The inclusion of this mechanism across several countries supports its possibilities in enhancing the results for this selected patient population.