A Case Report of Primary Resistance to EGFR TKI in Lung Adenocarcinoma Due to Coexisting MET Exon 14 Skipping Mutation with Excellent Response to Combination of Gefitinib and Capmatinib

Treatment of nonsmall cell lung cancer (NSCLC) carrying an epidermal growth factor receptor (EGFR) mutation depends on EGFR tyrosine kinase inhibitors (TKIs). However, all patients treated with EGFR TKI eventually develop progressive disease. Approximately, 20% of patients do not respond to EGFR TKIs, which is defined as primary resistance. The prognosis of these patients is similar to NSCLC with nondriver mutations. We report a case of a patient with EGFR exon 21 mutation who rapidly progressed in 15 days on Gefitinib. Next-generation sequencing (NGS) showed a MET exon 14 skip mutation coexisting with EGFR exon 21 mutation, causing primary resistance to EGFR TKI. Based on NGS reports, a treatment combining Gefitinib and Capmatinib, a MET inhibitor, induced a rapid response in the patient, which was sustained at the end of 8 months. This clearly emphasizes the need for comprehensive genomic profiling using NGS over single gene testing.