Choueiri Toni K, Halabi Susan, Sanford Ben L, Hahn Olwen, Michaelson M Dror, Walsh Meghara K, Feldman Darren R, Olencki Thomas, Picus Joel, Small Eric J, Dakhil Shaker, George Daniel J, Morris Michael J
Toni K. Choueiri and Meghara K. Walsh, Dana-Farber Cancer Institute; M. Dror Michaelson, Massachusetts General Hospital Cancer Center, Boston, MA; Susan Halabi and Ben L. Sanford, Alliance Statistics and Data Center and Duke University; Daniel J. George, Duke Cancer Institute, Duke University Medical Center, Durham, NC; Olwen Hahn, Alliance Protocol Operations Office, Chicago, IL; Darren R. Feldman and Michael J. Morris, Memorial Sloan Kettering Cancer Center, New York, NY; Thomas Olencki, Ohio State University Medical Center, Columbus, OH; Joel Picus, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO; Eric J. Small, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA; and Shaker Dakhil, University of Kansas Wichita, Wichita, KS.
J Clin Oncol. 2017 Feb 20;35(6):591-597. doi: 10.1200/JCO.2016.70.7398. Epub 2016 Nov 14.
Purpose 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. Patients and Methods 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. Results 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 33% (95% CI, 23 to 44) for cabozantinib versus 12% (95% CI, 5.4 to 21) 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%). Conclusion 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.
目的 卡博替尼是一种口服的强效血管内皮生长因子受体2、MET和AXL抑制剂，是转移性肾细胞癌（mRCC）的标准二线治疗药物。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患者一线治疗的疗效。
患者与方法 符合条件的患者为未经治疗的透明细胞mRCC，东部肿瘤协作组体能状态为0至2，根据国际转移性肾细胞癌数据库联盟标准为中危或低危。患者按1:1的比例随机分配至卡博替尼组（60 mg，每日1次）或舒尼替尼组（50 mg，每日1次；服药4周，停药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。
结果 2013年7月至2015年4月，157例患者被随机分组（卡博替尼组，n = 79；舒尼替尼组，n = 78）。与舒尼替尼相比，卡博替尼治疗显著延长了中位PFS（8.2个月对5.6个月），并使疾病进展或死亡风险降低了34%（校正风险比，0.66；95%CI，0.46至0.95；单侧P = 0.012）。卡博替尼的ORR为33%（95%CI，23%至44%），舒尼替尼为12%（95%CI，5.4%至21%）。所有原因导致的3级或4级不良事件在卡博替尼组为67%，舒尼替尼组为68%，包括腹泻（卡博替尼组10%对舒尼替尼组11%）、疲劳（6%对15%）、高血压（28%对22%）、手足红斑性感觉异常（8%对4%）和血液学不良事件（3%对22%）。
结论 在中危或低危mRCC患者中，作为一线治疗药物，卡博替尼在PFS和ORR方面比标准治疗药物舒尼替尼显示出显著的临床获益。
