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 Deep Fryer Filter Pots 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 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 Knitwear mutation and a PD-L1 TPS score of 75%.She received a salvage regime consisting of gefitinib, 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.