EGFR-TKIs plus chemotherapy demonstrated superior efficacy than EGFR-TKIs alone as first-line setting in advanced NSCLC patients with EGFR mutation and BIM deletion polymorphism

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2018-06, Vol.120, p.82-87
• Main Authors: Liu, Sangtian, He, Yayi, Jiang, Tao, Ren, Shengxiang, Zhou, Fei, Zhao, Chao, Li, Xuefei, Zhang, Jie, Su, Chunxia, Chen, Xiaoxia, Cai, Weijing, Gao, Guanghui, Li, Wei, Wu, Fengying, Li, Jiayu, Zhao, Jing, Hu, Qiong, Zhao, Mingchuan, Zhou, Caicun, Hirsch, Fred R.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bcl-2-Like Protein 11 - genetics; BIM deletion polymorphism; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - mortality; Chemotherapy; EGFR tyrosine kinase inhibitor; Epidermal growth factor receptor mutation; ErbB Receptors - genetics; Female; Genotype; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Male; Middle Aged; Mutation - genetics; Neoplasm Staging; Non-small-cell lung cancer; Protein Kinase Inhibitors - therapeutic use; Retrospective Studies; Survival Analysis
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2018.04.004

•BIM deletion polymorphism was a prognostic factor to the therapy of EGFR-TKIs.•EGFR-TKIs plus chemotherapy could improve BIM deletion polymorphism mediated intrinsic resistance to TKIs.•EGFR-TKIs plus chemotherapy showed better outcome in NSCLC patients with BIM deletion polymorphism. Non–small-cell lung cancer (NSCLC) patients with both epidermal growth factor receptor (EGFR) positive mutation and B-cell chronic lymphocytic leukemia/lymphoma-like 11 (BIM) deletion polymorphism had a poor clinical response to EGFR-tyrosine kinase inhibitors (TKIs). The current study aimed to investigate the clinical efficacy and tolerability of EGFR-TKIs plus chemotherapy versus EGFR-TKIs alone as first-line treatment in advanced NSCLC patients with EGFR mutations and BIM deletion polymorphism. A retrospective, non-randomized analysis was conducted. BIM deletion polymorphism was detected using polymerase chain reaction (PCR) analysis and direct sequencing of DNA from peripheral blood cells. Clinical characteristics, overall survival (OS), progress-free-survival (PFS), objective response rate (ORR) and treatment-related adverse events were compared between EGFR-TKIs alone versus EGFR-TKIs plus chemotherapy group. 65 patients were enrolled. 36 of them received EGFR-TKIs and 29 received EGFR-TKIs plus chemotherapy. EGFR-TKIs plus chemotherapy had significantly higher ORR than TKIs alone (65.5% vs. 38.9%, P = 0.046). Median PFS was significantly longer in EGFR-TKIs plus chemotherapy group than in TKIs group (7.2 vs 4.7 m; P = 0.008). Median OS was numerically longer in EGFR-TKIs plus chemotherapy group than in TKIs alone (18.5 vs 14.2 m; P = 0.107). EGFR-TKIs plus chemotherapy was associated with more grade 3 or 4 hematological toxic effects than EGFR-TKIs alone. EGFR-TKIs plus chemotherapy conferred a significantly higher ORR, prolonged PFS and numerically longer OS in advanced NSCLC patients with EGFR mutation and BIM deletion polymorphism. Further prospective studies are needed to validate these findings.