Zheng Zhen, Jin Xiance, Lin Baochai, Su Huafang, Chen Hanbin, Fei Shaoran, Zhao Lihao, Deng Xia, Xie Deyao, Xie Congying
Department of Radiotherapy and Chemotherapy, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China, 325000.
Department of Thoracic Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China, 325000.
J Cancer. 2017 Feb 15;8(4):597-605. doi: 10.7150/jca.16959. eCollection 2017.
Although superior clinical benefits of first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the treatment of advanced non-small-cell lung cancer (NSCLC) had been reported with different sensitivity, the sensitivity of second-line TKIs in NSCLC patients with different EFGR mutations was unknown. The purpose of this study is to investigate the clinical outcome of second-line EGFR-TKIs in the treatment of NSCLC patients according to different EGFR genotypes. The treatment outcomes of 166 NSCLC patients with different EGFR mutations treated by second-line TKIs were retrospectively reviewed. The efficacy was evaluated with Pearson chi-square or Fisher's exact tests, Log-rank test and Cox proportional hazards model. The disease control rate (DCR) and objective response rate (ORR) of enrolled NSCLC patients were 77.7% and 11.4%, respectively. The exon 19 deletion group had a significantly longer median progression-free survival (PFS) (6.7 vs. 4.5 months, P=0.002) and overall survival (OS) (13.7 vs. 11.7 months, P=0.02) compared with the exon 19 L858R mutation group for NSCLC patients, as well for patients with brain metastasis [PFS: (6.7 vs. 3.9 months, p<0.001), OS: (13.7 vs. 7.9 months, p=0.006)]. No significant difference on PFS and OS was observed between exon 19 deletion and L858R mutation group for patients with bone metastasis. EGFR genotype and ECOG PS were independent predictors of PFS. Never smoking, exon 19 deletion, EGOC PS (0-1) and no brain metastasis were correlated with longer OS. No significant difference on side effect between exon 19 and 21 mutation group was observed. NSCLC patients harboring exon 19 deletion achieved better PFS and OS than those with L858R mutation, indicating that EGFR mutation is a significant prognostic factor for advanced NSCLC patients with and without brain metastasis receiving second-line EGFR-TKIs treatment.
尽管一线表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKIs）在治疗晚期非小细胞肺癌（NSCLC）方面具有不同敏感性的卓越临床益处已被报道，但二线TKIs在不同EGFR突变的NSCLC患者中的敏感性尚不清楚。本研究的目的是根据不同的EGFR基因型，探讨二线EGFR-TKIs治疗NSCLC患者的临床结局。回顾性分析了166例接受二线TKIs治疗的不同EGFR突变的NSCLC患者的治疗结局。采用Pearson卡方检验或Fisher精确检验、Log-rank检验和Cox比例风险模型评估疗效。纳入的NSCLC患者的疾病控制率（DCR）和客观缓解率（ORR）分别为77.7%和11.4%。与外显子19 L858R突变组相比，外显子19缺失组的NSCLC患者以及脑转移患者的中位无进展生存期（PFS）显著更长（6.7个月对4.5个月，P=0.002）和总生存期（OS）显著更长（13.7个月对11.7个月，P=0.02）[PFS：（6.7个月对3.9个月，p<0.001），OS：（13.7个月对7.9个月，p=0.006）]。骨转移患者的外显子19缺失组和L858R突变组在PFS和OS方面未观察到显著差异。EGFR基因型和ECOG PS是PFS的独立预测因素。从不吸烟、外显子19缺失、EGOC PS（0-1）和无脑转移与更长的OS相关。外显子19和21突变组在副作用方面未观察到显著差异。携带外显子19缺失的NSCLC患者比L858R突变患者获得了更好的PFS和OS，表明EGFR突变是接受二线EGFR-TKIs治疗的有或无脑转移的晚期NSCLC患者的一个重要预后因素。
