T790M mutation is associated with better efficacy of treatment beyond progression with EGFR-TKI in advanced NSCLC patients

• Published in: Lung cancer (Amsterdam, Netherlands) Vol. 84; no. 3; pp. 295 - 300
• Main Authors: Li, Wei, Ren, Shengxiang, Li, Jiayu, Li, Aiwu, Fan, Lihong, Li, Xuefei, Zhao, Cao, He, Yayi, Gao, Guanghui, Chen, Xiaoxia, Li, Shuai, Shi, Jingyun, Zhou, Caicun, Fei, Ke, Schmid-Bindert, Gerald
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 01.06.2014
• Subjects: 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; Crown Ethers - therapeutic use; Disease Progression; DNA Mutational Analysis; Drug Resistance, Neoplasm - genetics; Erlotinib Hydrochloride; Female; Hematology, Oncology and Palliative Medicine; Humans; Kaplan-Meier Estimate; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Mutation; Pneumology; Polymerase Chain Reaction; Prognosis; Proportional Hazards Models; Protein Kinase Inhibitors - therapeutic use; Pulmonary/Respiratory; Quinazolines - therapeutic use; Receptor, Epidermal Growth Factor - genetics; Tumors; Tumors of the respiratory system and mediastinum; Secondary T790M mutation; EGFR-TKI; NSCLC; Acquired assistance; Human; Lung disease; Secondary; Prognosis; Acquired; Respiratory disease; Lung cancer; Patient; Malignant tumor; Epidermal growth factor receptor; Association; Treatment; Efficiency; Bronchus disease; Evolution; Advanced stage; Mutation; Cancer; Non small cell carcinoma
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2014.03.011

Abstract Background and purpose Continuous EGFR-TKI treatment beyond progression has shown promising benefit for some patients with acquired resistance to EGFR-TKIs. The aim of this study was to investigate the association of secondary T790M mutation at the time of progression with the efficacy of EGFR-TKI treatment beyond progression. Methods From March 2011 to March 2013, patients with advanced NSCLC who developed acquired resistance to EGFR-TKI and where a re-biopsy was performed at Tongji University Cancer Institute were included into this study. Scorpion ARMS was used to detect EGFR mutation status. Results A total of 54 patients were enrolled in this study with a median progression-free survival time (PFS1) of 10.9 months according to RECIST criteria. In all, 53.7% (29/54) had T790M mutation after the failure of EGFR-TKIs; PFS1 was not statistically significantly different between patients with T790M mutation and without (13.0 vs. 10.5 months, p = 0.894). In all, 41 patients received TKI treatment beyond progression, including 22 with local progression to receive additional local therapy and 19 with gradual progression to receive additional chemotherapy. The median progression-free survival time (PFS2) of patients who received EGFR-TKI beyond progression treatment was 3.5 months (95% CI, 2.689–4.311). Patients with T790M mutation had significantly longer PFS2 (6.3 vs. 2.6 months, p = 0.002) and overall survival (39.8 vs. 23.2 months, p = 0.044) than those without. Conclusion Patients with secondary T790M mutation at the time of progression having gradual or local progression after acquired resistance to EGFR-TKI benefit more from EGFR-TKI treatment beyond progression compared to those without T790M mutation.