title: Mutation abundance affects the efficacy of EGFR tyrosine kinase inhibitor readministration in non-small-cell lung cancer with acquired resistance.
abstract: There is no consensus in the salvage treatment for non-small-cell lung cancer (NSCLC) with acquired resistance to primary epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). Fifty-one consecutive EGFR-mutated NSCLC patients with TKI retreatment after acquired resistance were enrolled in this study. The quantitation of mutation abundance was performed by real-time fluorescent quantitative PCR. The correlation between mutation abundance and outcomes of readministrated TKI was analyzed by survival analysis. Patients with high (H) mutation abundance (24/51) had a significantly (log-rank, P < 0.05) longer (5.27-2.53 months) median progression-free survival (PFS), compared with the low (L) abundance group (27/51), whereas the median overall survival showed no difference (21.00-18.20 months, log-rank P = .403) between the two groups. Objective response and disease control rates in group H and group L regarding the second round TKI treatment were 8.3, 70.8 and 0, 48.1 %, respectively. Groupings with different mutation abundances were significantly associated with PFS under multivariate Cox proportional hazards regression model [hazard ratio (HR) for group H vs. L, 0.527; P = .036]. Mutation abundance affects the efficacy of EGFR-TKIs readministration in NSCLC with acquired resistance. The quantitative mutation abundance of EGFR may be a potential predictor for selecting optimal patients to readministrate EGFR-TKIs after acquired resistance to primary TKI.
authors: State Key Laboratory of Oncology in Southern China, Department of Thoracic Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors: Ze-Rui
authors: ZR
authors: Zhao
authors: Jin-Feng
authors: JF
authors: Wang
authors: Yong-Bin
authors: YB
authors: Lin
authors: Fang
authors: F
authors: Wang
authors: Sha
authors: S
authors: Fu
authors: Shu-Lin
authors: SL
authors: Zhang
authors: Xiao-Dong
authors: XD
authors: Su
authors: Long
authors: L
authors: Jiang
authors: Yi-Gong
authors: YG
authors: Zhang
authors: Jian-Yong
authors: JY
authors: Shao
authors: Hao
authors: H
authors: Long
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000627:therapeutic use; D012044:Regression Analysis; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D000077156:Gefitinib