Subscribe to RSS
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 CapmatinibFunding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
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.
Article published online:
19 July 2021
© 2021. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Thieme Medical and Scientific Publishers Private Ltd.
A-12, Second Floor, Sector -2, NOIDA -201301, India
- 1 Wu YL, Zhang L, Kim DW. et al. Phase Ib/II study of Capmatinib (INC280) plus Gefitinib after failure of epidermal growth factor receptor (EGFR) inhibitor therapy in patients with EGFR-mutated, MET factor-dysregulated non-small-cell lung cancer. J Clin Oncol 2018; 36 (31) 3101-3109
- 2 Schrock AB, Frampton GM, Suh J. et al. Characterization of 298 patients with lung cancer harboring MET Exon 14 skipping alterations. J Thorac Oncol 2016; 11 (09) 1493-1502
- 3 Awad MM, Oxnard GR, Jackman DM. et al. MET Exon 14 mutations in non-small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-Met overexpression. J Clin Oncol 2016; 34 (07) 721-730
- 4 Li W, Kang J, Zhang X. et al. Coexistence of MET exon 14 mutations with EGFR mutations in non-small cell lung cancer. J Clin Oncol 2017; 35 (15) e20636-e20636
- 5 Kauffmann-Guerrero D, Kahnert K, Kumbrink J, Syunyaeva Z, Tufman A, Huber RM. Successful treatment of a patient with NSCLC harboring an EGFR mutation and a concomitant Met Exon 14 skipping mutation combining Afatinib and Crizotinib. Clin Lung Cancer 2019; 20 (01) 59-62
- 6 Soria JC, Ohe Y, Vansteenkiste J. et al. FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med 2018; 378 (02) 113-125
- 7 Blakely CM, Watkins TBK, Wu W. et al. Evolution and clinical impact of co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancers. Nat Genet 2017; 49 (12) 1693-1704
- 8 Kim Y, Lee B, Shim JH. et al. Concurrent genetic alterations predict the progression to target therapy in EGFR-mutated advanced NSCLC. J Thorac Oncol 2019; 14 (02) 193-202