Cabozantinib Versus Sunitinib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN Trial.
Cabozantinib Versus Sunitinib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN Trial.
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DOI：
10.1200/jco.2016.70.7398
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发表时间：
2017-02-20
期刊：
影响因子：
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通讯作者：
Morris MJ
中科院分区：
文献类型：
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作者：
Choueiri TK;Halabi S;Sanford BL;Hahn O;Michaelson MD;Walsh MK;Feldman DR;Olencki T;Picus J;Small EJ;Dakhil S;George DJ;Morris MJ
卡博替尼是血管内皮生长因子受体2、MET和AXL的口服强效抑制剂，并且是转移性肾细胞癌（mRCC）的标准二线疗法。这项随机II期多中心试验评估了卡博替尼与舒尼替尼作为mRCC患者的一线治疗。符合条件的患者未经治疗的透明细胞mRCC和东部肿瘤协作组体能状态为0 - 2，并且根据国际转移性肾细胞癌数据库联盟标准为中等或较差风险。患者以一比一的比例随机分配到卡博替尼（60 mg，每天一次）或舒尼替尼（50 mg，每天一次; 4周，2周）。无进展生存期（PFS）是主要终点。客观缓解率（ORR）、总生存期和安全性是次要终点。从2013年7月至2015年4月，157名患者被随机分配（卡博替尼，n = 79;舒尼替尼，n = 78）。与舒尼替尼相比，卡博替尼治疗显著增加了中位PFS（8.2 vs 5.6个月），并与进展或死亡率降低34%相关（调整后的风险比，0.66; 95%CI，0.46至0.95;单侧P = 0.012）。卡博替尼的ORR为46%（95%CI，34至57），而舒尼替尼为18%（95%CI，10至28）。卡博替尼和舒尼替尼的全因3或4级不良事件分别为67%和68%，包括腹泻（卡博替尼，10%对舒尼替尼，11%），疲劳（6%对15%），高血压（28%对22%），掌跖红斑（8%对4%）和血液学不良事件（3%对22%）。卡博替尼在PFS和ORR方面表现出优于标准治疗舒尼替尼的显著临床益处，作为中等或低风险mRCC患者的一线治疗。
Cabozantinib is an oral potent inhibitor of vascular endothelial growth factor receptor 2, MET, and AXL and is a standard second-line therapy for metastatic renal cell carcinoma (mRCC). This randomized phase II multicenter trial evaluated cabozantinib compared with sunitinib as first-line therapy in patients with mRCC. Eligible patients had untreated clear cell mRCC and Eastern Cooperative Oncology Group performance status of 0 to 2 and were intermediate or poor risk per International Metastatic Renal Cell Carcinoma Database Consortium criteria. Patients were randomly assigned at a one-to-one ratio to cabozantinib (60 mg once per day) or sunitinib (50 mg once per day; 4 weeks on, 2 weeks off). Progression-free survival (PFS) was the primary end point. Objective response rate (ORR), overall survival, and safety were secondary end points. From July 2013 to April 2015, 157 patients were randomly assigned (cabozantinib, n = 79; sunitinib, n = 78). Compared with sunitinib, cabozantinib treatment significantly increased median PFS (8.2 v 5.6 months) and was associated with a 34% reduction in rate of progression or death (adjusted hazard ratio, 0.66; 95% CI, 0.46 to 0.95; one-sided P = .012). ORR was 46% (95% CI, 34 to 57) for cabozantinib versus 18% (95% CI, 10 to 28) for sunitinib. All-causality grade 3 or 4 adverse events were 67% for cabozantinib and 68% for sunitinib and included diarrhea (cabozantinib, 10% v sunitinib, 11%), fatigue (6% v 15%), hypertension (28% v 22%), palmar-plantar erythrodysesthesia (8% v 4%), and hematologic adverse events (3% v 22%). Cabozantinib demonstrated a significant clinical benefit in PFS and ORR over standard-of-care sunitinib as first-line therapy in patients with intermediate- or poor-risk mRCC.