Lin Ying, Wu Zheng, Zhang Jian, Hu Xichun, Wang Zhonghua, Wang Biyun, Cao Jun, Wang Leiping
1 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Tumour Biol. 2017 Jun;39(6):1010428317711033. doi: 10.1177/1010428317711033.
Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2. This study aimed to evaluate the efficacy and safety of apatinib in metastatic breast cancer (MBC) under non-clinical trial setting, and to study the impact of previous antiangiogenic treatment to the efficacy of apatinib. 52 MBC patients treated with apatinib under non-clinical trial setting in Fudan University Shanghai Cancer Center between January 1st 2015 and October 1st 2016 were included. All patients were included in time-to-treatment failure (TTF) analysis, while 45 patients were enrolled for progression-free survival (PFS) and overall survival (OS) analysis because 7 of the patients with treatment discontinuation due to intolerable toxicities had too short time for efficacy assessment. Impact of previous exposure to antiangiogenic treatment and other factors to patients' survival were analyzed by Log-rank analysis and Cox multivariate analysis. The median PFS, median OS, and median TTF were 4.90 (95% confidence interval [CI] 3.44 - 6.36), 10.3 (unable to calculate 95% CI), and 3.93 (95% CI 1.96 - 5.90) months, respectively. Previous treatment of bevacizumab did not affect the efficacy of apatinib. Previous exposure to anthracycline, age of 60 years or older and palmar-plantar erythrodysesthesia syndrome were independent predictors for prolonged PFS. Discontinuation of treatment was more common in age group of 60 years or older than that in younger group, although the difference was not significant. Although toxicities were generally managable, a previously unrecorded grade 3~4 adverse event of dyspnea has been observed. This study confirmed the encouraging efficacy and manageable safety of apatinib on pretreated MBC patients in non-clinical trial setting. For the first time to our knowledge, this study found that previous treatment of bevacizumab did not affect the efficacy of apatinib, and reported an undocumented severe adverse effect of dyspnea.
阿帕替尼是一种新型的靶向血管内皮生长因子受体2的酪氨酸激酶抑制剂。本研究旨在评估在非临床试验环境下阿帕替尼治疗转移性乳腺癌（MBC）的疗效和安全性，并研究既往抗血管生成治疗对阿帕替尼疗效的影响。纳入了2015年1月1日至2016年10月1日期间在复旦大学附属肿瘤医院于非临床试验环境下接受阿帕替尼治疗的52例MBC患者。所有患者均纳入治疗失败时间（TTF）分析，45例患者纳入无进展生存期（PFS）和总生存期（OS）分析，因为7例因无法耐受毒性而停药的患者进行疗效评估的时间过短。通过对数秩分析和Cox多因素分析既往抗血管生成治疗及其他因素对患者生存的影响。PFS中位数、OS中位数和TTF中位数分别为4.90个月（95%置信区间[CI] 3.44 - 6.36）、10.3个月（无法计算95%CI）和3.93个月（95%CI 1.96 - 5.90）。既往使用贝伐单抗治疗不影响阿帕替尼的疗效。既往使用蒽环类药物、年龄60岁及以上和手足红斑感觉异常综合征是PFS延长的独立预测因素。60岁及以上年龄组的治疗中断比年轻组更常见，尽管差异不显著。虽然毒性一般可控制，但观察到一种既往未记录的3~4级呼吸困难不良事件。本研究证实了在非临床试验环境下阿帕替尼对经治MBC患者具有令人鼓舞的疗效和可控制的安全性。据我们所知，本研究首次发现既往使用贝伐单抗治疗不影响阿帕替尼的疗效，并报告了一种未记录的严重不良反应——呼吸困难。
