Cabozantinib抑止酪氨酸激酶，包含毛细血管表皮细胞生长因子蛋白激酶1、2、3、MET和AXL,他们与肝细胞癌的进展及其对索拉菲尼的抗药性的发展趋势相关，它是末期病症的规范原始医治。这一任意的，双盲实验的，第三环节的实验评定了与安慰剂对比，cabozantinib在此前医治的末期肝细胞癌患者中的功效。
Cabozantinib inhibits tyrosine kinases, including vascular endothelial growth factor receptors 1, 2, and 3, MET, and AXL, which are implicated in the progression of hepatocellular carcinoma and the development of resistance to sorafenib, the standard initial treatment for advanced disease. This randomized, double-blind, phase 3 trial evaluated cabozantinib as compared with placebo in previously treated patients with advanced hepatocellular carcinoma.
方式
一共有707名患者按2:1的占比被任意分派到接纳Cabozantinib (每日60mg)或配对安慰剂组。满足条件的患者曾接纳过索拉菲尼的医治，在最少一次肝细胞癌的全身上下医治后发生病症进展，很有可能接纳过二种之上的末期肝细胞癌的全身上下计划方案。最关键的终点站是总体存活。主次终点站为无进展存活率和客观性反映率。
A total of 707 patients were randomly assigned in a 2:1 ratio to receive cabozantinib (60 mg once daily) or matching placebo. Eligible patients had received previous treatment with sorafenib, had disease progression after at least one systemic treatment for hepatocellular carcinoma, and may have received up to two previous systemic regimens for advanced hepatocellular carcinoma. The primary end point was overall survival. Secondary end points were progression-free survival and the objective response rate.
結果
在第二次方案的中后期剖析中，实验表明，与安慰剂对比，Cabozantinib的整体存活率显著更长。cabozantinib组均值总存活期为10.2个月，安慰剂组为8.0个月。cabozantinib组无进展存活期中位值为5.2个月，安慰剂组为1.9个月，客观性回复率各自为4%和不够1% (P = 0.009)。cabozantinib组68%的患者发生3级或四级不良反应，安慰剂组36%。最普遍的高级事情是掌跖红细胞觉得出现异常(17%用Cabozantinib,0%用安慰剂)，血压高(16%比2%)，天冬氨酸氨谷丙转氨酶水准上升(12%比7%)，疲惫(10%比4%)和拉肚子(10%比2%)。
At the second planned interim analysis, the trial showed significantly longer overall survival with cabozantinib than with placebo. Median overall survival was 10.2 months with cabozantinib and 8.0 months with placebo (hazard ratio for death, 0.76; 95% confidence interval [CI], 0.63 to 0.92; P=0.005). Median progression-free survival was 5.2 months with cabozantinib and 1.9 months with placebo (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.52; P<0.001), and the objective response rates were 4% and less than 1%, respectively (P=0.009). Grade 3 or 4 adverse events occurred in 68% of patients in the cabozantinib group and in 36% in the placebo group. The most common high-grade events were palmar�Cplantar erythrodysesthesia (17% with cabozantinib vs. 0% with placebo), hypertension (16% vs. 2%), increased aspartate aminotransferase level (12% vs. 7%), fatigue (10% vs. 4%), and diarrhea (10% vs. 2%).
结果
在之前医治过的末期肝细胞癌患者中，与安慰剂对比，Cabozantinib的医治能增加患者的总体存活率和无进展存活率。Cabozantinib组的高风险事情发病率大概是安慰剂组的二倍。
Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo. The rate of high-grade adverse events in the cabozantinib group was approximately twice that observed in the placebo group. (Funded by Exelixis; CELESTIAL ClinicalTrials.gov number, NCT01908426.)
