Bisphosphonates enhance EGFR-TKIs efficacy in advanced NSCLC patients with EGFR activating mutation: A retrospective study.
Bisphosphonates enhance EGFR-TKIs efficacy in advanced NSCLC patients with EGFR activating mutation: A retrospective study.
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双磷酸盐可增强 EGFR-TKIs 对具有 EGFR 激活突变的晚期 NSCLC 患者的疗效：一项回顾性研究
DOI：
10.18632/oncotarget.5515
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发表时间：
2016-10-11
期刊：
影响因子：
--
通讯作者：
Wang YS
中科院分区：
文献类型：
--
作者：
Huang CY;Wang L;Feng CJ;Yu P;Cai XH;Yao WX;Xu Y;Liu XK;Zhu WJ;Wang Y;Zhou J;Lu Y;Wang YS
背景双膦酸盐在非小细胞肺癌(NSCLC)中表现出抗肿瘤活性。我们的目的是评估双膦酸类药物与EGFR酪氨酸激酶抑制剂(EGFR-TKIs)联合应用是否能对伴有EGFR突变的晚期非小细胞肺癌患者产生协同作用。方法从2008年1月至2013年10月，从两个癌症中心收集114例接受EGFR-TKI一线治疗的晚期EGFR突变非小细胞肺癌患者。将患者分为EGFR-TKIs组和EGFR-TKIs+双磷酸盐(联合)组。分析中位无进展生存期(MPFS)、中位总生存期(MOS)分布及生存曲线。结果114例患者中有62例发生骨转移，其中19例接受EGFR-TKIs治疗，43例接受EGFR-TKIs+双磷酸盐治疗。骨转移患者中位PFS和OS较EGFR-TKIs组明显改善(MPFS：15.0vs7.3月，P=0.0017；MOS：25.2月vs10.4个月，P=0.0015)。71例(19例骨转移)患者中，骨转移患者的生存预后较差(MFS：7.3月vs12.1月，P=0.0434；MOS：10.4月vs22.0月，P=0.0036)。接受EGFR-TKIs联合双膦酸盐治疗的骨转移患者的生存期不低于单用EGFR-TKIs的非骨转移患者(MPFS：15.0vs12.1个月，p=0.1871；MOS：25.2月vs22.0月，p=0.9798)。结论联合应用双膦酸类药物和EGFR-TKIs可提高EGFR突变并伴有骨转移的非小细胞肺癌患者的治疗效果和生存质量。
Background Bisphosphonates have exhibited anti-tumor activity in non-small cell lung cancer (NSCLC). We aimed to evaluate whether the combination of bisphosphonates with tyrosine kinase inhibitors of EGFR (EGFR-TKIs) could obtain a synergistic effect on advanced NSCLC patients with EGFR mutations. Methods Between January 2008 and October 2013, 114 advanced EGFR mutations NSCLC patients who received EGFR-TKIs as first-line therapy were recruited from two cancer centers. Patients were separated into EGFR-TKIs alone or EGFR-TKIs plus bisphosphonates (combination) group. Median progression free survival (mPFS), median overall survival (mOS) distributions and survival curves were analyzed. Results Among the 114 patients, 62 had bone metastases (19 patients treated with EGFR-TKIs, 43 patients treated with EGFR-TKIs + bisphosphonates). Median PFS and OS were significantly improved in combination group compared with EGFR-TKIs group (mPFS: 15.0 vs 7.3 months, P = 0.0017; mOS: 25.2 vs 10.4 months, P = 0.0015) in patients with bone metastases. Among the 71 patients (19 patients with bone metastases) treated with EGFR-TKIs alone, patients with bone metastases had poor survival prognosis (mPFS:7.3 vs 12.1 months, P = 0.0434; mOS:10.4 vs 22.0 months, P = 0.0036). The survival of patients with bone metastases who received EGFR-TKIs plus bisphosphonates therapy was non-inferior to patients without bone metastases treated with EGFR-TKIs alone (mPFS: 15.0 vs 12.1 months, p = 0.1871; mOS: 25.2 vs 22.0 months, p = 0.9798). Conclusions Concomitant use of bisphosphonates and EGFR-TKIs improves therapeutic efficacy and brings survival benefits to NSCLC patients with EGFR mutation and bone metastases.