Clinical implications of T790M mutation in patients with acquired resistance to EGFR tyrosine kinase inhibitors

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2013-11, Vol.82 (2), p.294-298
• Main Authors: Sun, Jong-Mu, Ahn, Myung-Ju, Choi, Yoon-La, Ahn, Jin Seok, Park, Keunchil
• Format: Article
• Language: English
• Subjects: Afatinib; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Codon; Disease Progression; Drug Resistance, Neoplasm - genetics; Epidermal growth factor receptor; Female; Hematology, Oncology and Palliative Medicine; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Medical sciences; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Mutation - drug effects; Neoplasm Staging; Pneumology; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Pulmonary/Respiratory; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - genetics; Resistance; Risk Factors; T790M; Treatment Outcome; Tumors; Tumors of the respiratory system and mediastinum; Tyrosine kinase inhibitor
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2013.08.023

Abstract Objectives Although T790M mutation is considered to be the major mechanism of acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC), its clinical implication remains undetermined. Methods Post-progression tumor specimens were prospectively collected for T790M mutation analysis in NSCLC patients with acquired resistance to initial EGFR TKIs. Clinical features were compared between patients with and without T790M. Results Out of 70 cases, 36 (51%) were identified to have T790M mutation in the rebiopsy specimen. There was no difference in the pattern of disease progression, progression-free survival for initial TKIs (12.8 and 11.3 months), post-progression survival (14.7 and 14.1 months), or overall survival (43.5 and 36.8 months) in patients with and without T790M. In total, 34 patients received afatinib after post-progression biopsy as a subsequent treatment, and the response rate was 18%. The median progression-free survival for afatinib was 3.7 months for the entire group, and 3.2 and 4.6 months for the groups with and without T790M, respectively ( P = 0.33). Conclusions The identification of T790M as acquired resistance mechanism was clinically feasible. Although T790M had no prognostic or predictive role in the present study, further research is necessary to identify patients with T790M-mutant tumors who might benefit from newly developed T790M-specific TKIs.