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2015泌尿生殖系统肿瘤研讨会（ASCO GU）于2月26日至28日在美国奥兰多举行。此次会议由美国临床肿瘤学会（ASCO），美国放射肿瘤学会（ASTRO），泌尿肿瘤协会（SUO）联合举办。重点关注了前列腺癌，肾癌，睾丸癌等在预防、筛查及诊疗方面的最新进展。医脉通将陆续对会议内容进行报道。
Cabozantinib(Cabo) 可抑制包括MET和VEGFRs在内的酪氨酸激酶。在会上展出的关于转移性去势抵抗性前列腺癌（mCRPC）的2期临床研究COMET-1显示，Cabo与骨骼扫描缓解，疼痛、可测量疾病及循环肿瘤细胞的改善相关。COMET-1试验在经多西他赛、阿比特龙和/或恩杂鲁胺治疗的进展期转移性去势抵抗性前列腺癌患者中，对比了Cabo与泼尼松治疗在总生存方面的差异。（摘要号139）
在这项随机、双盲，3期对照研究中(NCT01605227)，经多西他赛、阿比特龙和/或恩杂鲁胺治疗的转移性去势抵抗性前列腺癌患者被随机按2:1比例分配，接受Cabo (60 mg qd)或泼尼松(5 mg bid)治疗。按之前接受的卡巴他赛治疗，ECOG状态，及中度至重度疼痛对患者进行分层。研究的首要终点为OS。研究观察到578例死亡时，90%的统计效能检测到的风险比为0.75。次要研究终点是通过独立放疗委员会测定的12周时骨骼扫描缓解(BSR)。定义为：与基线相比，骨骼扫描病灶区域有≥30%的减少。试探性的终点包括PFS和OS亚组分析。
该研究在2012年7月至2013年11月之间共招募了1028位患者。614例死亡后进行的最终分析中，Cabo组的中位OS估计值为11.0个月，泼尼松的中位OS估计值为9.8个月(HR 0.90; 95% CI: 0.0.76-1.06; P = 0.212)。
Cabo组的次要终点BSR为41%，泼尼松组为3%(P <0.001)。两组的中位PFS分别为：Cabo组5.5个月 vs 泼尼松组2.8个月 (HR 0.50; P <0.001)。Cabo组中有内脏疾病的191位患者的中位OS为7.1个月，泼尼松组为4.8个月(HR 0.65; P = 0.0215)。
Cabo组的371 (54.4%)位患者及泼尼松组的233(67.3%)位患者接受了解救治疗。Cabo组中的107 (15.7%)位患者及泼尼松组中的104 (30.1%)位患者接受了卡巴他赛和/或多西他赛治疗。
Cabo组较泼尼松组更常见的严重不良反应事件包括肺栓塞，恶心，脱水及疲劳。
与泼尼松相比，Cabo提高了BSR和PFS，但没有显著提高OS。在内脏转移患者亚组中，OS的改善最显著。Cabo的活性和安全性与转移性去势抵抗性前列腺癌的2期研究中观察到的相似。临床试验信息：NCT01605227
英文摘要
Background: Cabo inhibits tyrosine kinases including MET and VEGFRs. In a phase 2 study in mCRPC pts, Cabo was associated with improvements in bone scans, pain, measurable disease, and circulating tumor cells. COMET-1 compared the effects of Cabo versus Pred on overall survival (OS) in men with progressive mCRPC and prior D and A and/or E.
Methods: In this randomized, double-blind, controlled phase 3 study (NCT01605227), pts with mCRPC and prior D and A and/or E were randomized 2:1 to receive Cabo (60 mg qd) or Pred (5 mg bid). Pts were stratified by prior treatment with cabazitaxel, ECOG status, and presence of moderate to severe pain. The primary endpoint was OS. The study was designed to observe 578 deaths to provide 90% power to detect a hazard ratio (HR) of 0.75. A secondary endpoint was bone scan response at Week 12 (BSR) determined by central independent radiology committee, defined as a ≥30% decrease in the bone scan lesion area compared to baseline. Exploratory endpoints include PFS and OS subgroup analyses.
Results: 1,028 pts were randomized between Jul 2012 and Nov 2013. In the final analysis after 614 deaths, the estimated median OS was 11.0 months for Cabo vs 9.8 months for Pred (HR 0.90; 95% CI: 0.0.76-1.06; P = 0.212). The secondary endpoint of BSR was 41% for Cabo vs 3% for Pred (P <0.001). Median PFS per investigator was 5.5 months for Cabo vs 2.8 months for Pred (HR 0.50; P <0.001). For 191 pts with visceral disease median OS was 7.1 months for Cabo vs 4.8 months for Pred (HR 0.65; P = 0.0215). 371 (54.4%) and 233 (67.3%) pts received salvage therapy in the Cabo and Pred arms, respectively. Subsequent cabazitaxel and/or D was reported in 107 (15.7%) and 104 (30.1%) Cabo and Pred pts, respectively. Serious adverse events of pulmonary embolism, nausea, dehydration and fatigue were more frequent with Cabo.
Conclusions: Compared to prednisone, Cabo improved BSR and PFS but did not significantly increase OS. The improvement in OS was greatest in the subset of patients with visceral metastases. The activity and safety profile of Cabo was similar to that observed in phase 2 studies in mCRPC. Clinical trial information: NCT01605227
