Osimertinib and Capmatinib Combination Therapy to Overcome MET Y1003N-Mediated Resistance in EGFR-Mutant NSCLC: A Case Report

Osimertinib, a third-generation EGFR tyrosine kinase inhibitor, is the frontline standard in the treatment of metastatic EGFR-mutant NSCLC. Although osimertinib is effective, disease progression occurs in virtually all patients, mediated by a heterogeneous array of resistance mechanisms. Activation of the MET signaling pathway by means of amplification has been implicated in resistance to osimertinib, but activation caused by point mutations in MET has not been well described. Here, we present the case of a 65-year-old female with metastatic EGFR-mutant NSCLC whose disease progressed on osimertinib owing to emergence of MET Y1003N mutation. She subsequently received capmatinib in combination with osimertinib and achieved a partial response. This case illustrates a potential role for dual EGFR/MET inhibition in EGFR-mutated NSCLC with resistance driven by activating MET mutations.