Efficacy and Safety of Dovitinib in Pretreated Patients With Advanced Squamous Non-Small Cell Lung Cancer With FGFR1 Amplification: A Single-Arm, Phase 2 Study
Efficacy and Safety of Dovitinib in Pretreated Patients With Advanced Squamous Non-Small Cell Lung Cancer With FGFR1 Amplification: A Single-Arm, Phase 2 Study
复制标题
DOI：
10.1002/cncr.30135
复制
发表时间：
2016-10-01
期刊：
影响因子：
6.2
通讯作者：
Ahn, Myung-Ju
中科院分区：
文献类型：
--
作者：
Lim, Sung Hee;Sun, Jong-Mu;Ahn, Myung-Ju
成纤维细胞生长因子受体1（FGFR 1）扩增肺鳞状细胞癌（SCC）中的潜在驱动癌基因。目前的II期研究评估了Dovitinib（一种FGFR抑制剂）在晚期肺SCC患者中的疗效和耐受性。方法：采用荧光原位杂交技术，对经预处理的晚期肺鳞癌患者的肿瘤进行检测，结果显示FGFR 1扩增> 5拷贝。每周第1 - 5天口服Dovitinib 500 mg，每日一次，随后停药2天。主要终点为总体缓解。次要终点是无进展生存期、总生存期和毒性。结果所有26例患者均为男性，中位年龄为68岁（范围52-80岁）。大多数患者是曾经吸烟者。dovitinib给药的中位持续时间（每周期28天）为2.5个月（范围：0.7-8.6个月）。总缓解率为11.5%（95%置信区间[95% CI]，0.8%-23.8%），疾病控制率为50%（95% CI，30.8%-69.2%），3例患者达到部分缓解。部分缓解患者的缓解持续时间分别为≥ 4.5个月、≥ 5.1个月和6.1个月。中位随访15.7个月（范围：1.2-25.6个月）后，中位总生存期为5.0个月（95% CI，3.6-6.4个月），中位无进展生存期为2.9个月（95% CI，1.5-4.3个月）。最常见的3级或以上不良事件为疲乏（19.2%）、厌食（11.5%）和低钠血症（11.5%）（事件严重程度根据美国国家癌症研究所不良事件通用术语标准[版本4.0]分级）。结论：dovitinib治疗在伴有FGFR 1扩增的晚期SCC患者中表现出适度的疗效。需要进一步研究以评估与dovitinib在SCC患者中的疗效相关的其他生物标志物。(C)2016美国癌症协会
BACKGROUND Fibroblast growth factor receptor 1 (FGFR1) amplifications a potential driving oncogene in squamous cell cancer (SCC) of the lung. The current phase 2 study evaluated the efficacy and tolerability of dovitinib, an FGFR inhibitor, in patients with advanced SCC of the lung. METHODS Patients with pretreated advanced SCC of the lung whose tumors demonstrated FGFR1 amplification of > 5 copies by fluorescence in situ hybridization were enrolled. Dovitinib at a dose of 500 mg was administered orally, once daily, on days 1 to 5 of every week, followed by 2 days off. The primary endpoint was overall response. Secondary endpoints were progression-free survival, overall survival, and toxicity. RESULTS All 26 patients were men with a median age of 68 years (range, 52-80 years). The majority of patients were ever-smokers. The median duration of dovitinib administration (28 days per cycle) was 2.5 months (range, 0.7-8.6 months). The overall response rate was 11.5% (95% confidence interval [95% CI], 0.8%-23.8%) and the disease control rate was 50% (95% CI, 30.8%-69.2%), with 3 patients achieving partial responses. Response durations for the patients with partial responses were >= 4.5 months, >= 5.1 months, and 6.1 months, respectively. After a median follow-up of 15.7 months (range, 1.2-25.6 months), the median overall survival was 5.0 months (95% CI, 3.6-6.4 months) and the median progression-free survival was 2.9 months (95% CI, 1.5-4.3 months). The most common grade 3 or higher adverse events were fatigue (19.2%), anorexia (11.5%), and hyponatremia (11.5%) (event severity was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). CONCLUSIONS Treatment with dovitinib demonstrated modest efficacy in patients with advanced SCC with FGFR1 amplification. Further studies to evaluate other biomarkers correlated with the efficacy of dovitinib in patients with SCC are warranted. (C) 2016 American Cancer Society.