EGFR plus MET targeted therapies for overcoming treatment resistance in EGFR mutant NSCLC. A Case Report.

INTRODUCTION Oncogenic-addicted non-small cell lung cancer (NSCLC) has emerged as the most prevalent form of lung cancer, presenting a dynamic landscape in treatment modalities. Among these, epidermal growth factor receptor (EGFR)-mutant NSCLC remains the predominant oncogenic mutation, particularly prevalent in regions such as Asia and Latin America. CASE PRESENTATION This case study highlights the experience of a woman diagnosed with EGFR-sensitive (del exon 19) mutant NSCLC who demonstrated an extended duration of response (DOR) to third-generation EGFR-TKI therapy. Upon disease progression, detection of MET gene amplification prompted the addition of a selective MET inhibitor to the existing EGFR-TKI regimen, resulting in a complete response for the patient. DISCUSSION/CONCLUSION The molecular heterogeneity of this condition has significantly increased in complexity over recent years, marked by the identification of baseline co-alterations and development of a broad spectrum of resistance mechanisms post-EGFR tyrosine kinase inhibitor (TKI) therapy. This complexity poses a substantial challenge to clinicians. Despite the rapid advancement of targeted therapies and the implementation of treatment escalation through combination strategies, there remains an ongoing debate regarding which patients would benefit most from combination therapies, both in the initial treatment phase and in the setting of disease progression, particularly when off-target resistance mechanisms or co-alterations are identified.