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.
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 NSCLCpatients 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.
Authors: Daria Gaut; Myung Shin Sim; Yuguang Yue; Brian R Wolf; Phillip A Abarca; James M Carroll; Jonathan W Goldman; Edward B Garon Journal: Clin Lung Cancer Date: 2017-06-20 Impact factor: 4.785
Authors: Hyungjin Kim; Kum Ju Chae; Soon Ho Yoon; Miso Kim; Bhumsuk Keam; Tae Min Kim; Dong-Wan Kim; Jin Mo Goo; Chang Min Park Journal: Eur Radiol Date: 2017-08-07 Impact factor: 5.315
Authors: Evangelos Tsiambas; Nicholas S Mastronikolis; Alicia Y Lefas; Stavros N Georgiannos; Vasileios Ragos; Panagiotis P Fotiades; Nikolaos Tsoukalas; Nikolaos Kavantzas; Andreas Karameris; Dimitrios Peschos; Efstratios Patsouris; Konstantinos Syrigos Journal: In Vivo Date: 2017 Jul-Aug Impact factor: 2.155
Authors: Karthick Vishwanathan; Paul A Dickinson; Karen So; Karen Thomas; Yuh-Min Chen; Javier De Castro Carpeño; Anne-Marie C Dingemans; Hye Ryun Kim; Joo-Hang Kim; Matthew G Krebs; James Chih-Hsin Yang; Khanh Bui; Doris Weilert; R Donald Harvey Journal: Br J Clin Pharmacol Date: 2018-03-23 Impact factor: 4.335