Case Report: Sequential Combination Targeted Therapy With Type I and II MET Inhibitors in a Metastatic EGFR-Mutated, MET-Amplified NSCLC Patient With Acquired MET Y1230H Mutation

Case Report: Sequential Combination Targeted Therapy With Type I and II MET Inhibitors in a Metastatic EGFR-Mutated, MET-Amplified NSCLC Patient With Acquired MET Y1230H Mutation

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Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the standard of care for advanced non-small-cell lung cancer (NSCLC) patients.However, most patients will eventually develop resistance.For EGFR-TKI resistance mediated by MET amplification, the combination of EGFR and MET TKIs has shown promising results in early clinical trials.

However, acquired resistance to MET inhibitors forms a formidable challenge to this dual blockade approach.Here, we presented an NSCLC patient with EGFR exon 19 deletion (ex19del) who was resistant altitude sunscreen to first-line erlotinib treatment but responded to chemotherapy.Given the finding of MET overexpression/amplification after disease progression, the patient received gefitinib plus crizotinib with a partial response.

Her disease progressed again, and molecular testing revealed a novel MET Y1230H mutation and a PD-L1 TPS score of 75%.She received a salvage regime consisting of gefitinib, icon track bar f250 cabozantinib, and pembrolizumab with a partial response.Since we now know that EGFR ex19del NSCLC patients generally do not respond to PD-1 blockade therapy, this response is more likely the contribution from gefitinib plus cabozantinib.

Therefore, sequential use of type I and II MET inhibitors in EGFR/MET dual blockade may be an effective therapeutic option for EGFR-mutant, MET-amplified NSCLC.