WCLC 2025 - Posters & ePosters-EP.12.50 Tepotinib Plus an EGFR Tyrosine Kinase Inhibitor as an Effective Subsequent Line: A Case Series From Kuwait

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This case series from Kuwait Cancer Control Center reports on three patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC) who developed resistance to first-line Osimertinib therapy due to MET amplification, a known mechanism of acquired resistance. Combining Tepotinib, a highly selective MET tyrosine kinase inhibitor (TKI), with Osimertinib was investigated as a subsequent line of treatment.<br /><br />The patients, aged 46-74, received Tepotinib plus Osimertinib following progression on Osimertinib alone. Results showed effective control of extracranial disease with manageable side effects, mainly dermatologic and hematologic. Radiologic assessments via PET-CT scans demonstrated metabolic responses and disease stabilization in systemic sites, although central nervous system (CNS) progression remained a challenge due to Tepotinib's limited CNS penetration. Local therapies and CNS monitoring were necessary components of patient management.<br /><br />Key findings emphasize the importance of re-biopsy and molecular profiling after Osimertinib resistance to guide treatment decisions. The Tepotinib-Osimertinib combination showed promising systemic efficacy in MET amplification-driven resistance, underscoring the value of precision medicine tailored to evolving tumor biology. The report advocates for multidisciplinary approaches to optimize treatment outcomes for complex metastatic NSCLC.<br /><br />The authors call for further research to overcome resistance mechanisms, including development of CNS-penetrant MET inhibitors and prospective clinical trials. They highlight the need for biomarker-driven sequencing algorithms and real-world data, especially in the MENA region where EGFR mutations occur in about 24% of NSCLC cases. Compassionate use programs may expand access and generate additional evidence.<br /><br />In summary, this case series supports Tepotinib plus Osimertinib as an effective treatment strategy for MET amplification-mediated Osimertinib resistance, providing clinical benefits in patients with poor prognosis while identifying critical areas for future research and comprehensive care models.

Asset Subtitle

Abdulaziz AlJassim AlShareef

Meta Tag

Speaker Abdulaziz AlJassim AlShareef

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

EGFR-mutant NSCLC

Osimertinib resistance

MET amplification

Tepotinib

Tyrosine kinase inhibitor

Combination therapy

Central nervous system progression

Molecular profiling

Precision medicine

MENA region lung cancer