Robert J. Motzer, Memorial Sloan-Kettering Cancer Center, New York, NY; Dmitry Nosov, N.N. Blokhin Cancer Research Center; Boris Y. Alekseev, Federal State Institution, Moscow Research Oncological Institute, Moscow; Oleg Lipatov, State Budget Medical Institution, Republican Clinical Oncological Center, Bashkortostan; Anna Alyasova, Federal Budget Medical Institution, Privolzhsky District Medical Center, Nizhny Novgorod; Mikhail Kogan, State Budget Higher Educational Institute, The Rostov State Medical University, Rostov-on-Don, Russia; Timothy Eisen, Cambridge University Health Partners, Cambridge, United Kingdom; Igor Bondarenko, Dnipropetrovsk State Medical Academy under the Ministry of Health of Ukraine, Dnipropetrovsk; Vladimir Lesovoy, V.I. Shapoval Regional Clinical Center for Urology and Nephrology, Kharkiv; Oleksiy Lyulko, Zaporizhia Medical Academy of Postgraduate Education, Zaporizhia, Ukraine; Piotr Tomczak, Clinical Hospital No. 1 of the Poznan University of Medical Sciences, Poznań; Cezary Szczylik, Military Institute of Health, Warsaw, Poland; Mihai Harza, Fundeni Clinical Institute, Bucharest, Romania; Cora N. Sternberg, San Camillo and Forlanini Hospitals, Rome, Italy; David Cella, Northwestern University Feinberg School of Medicine, Chicago; Andrew Krivoshik, Astellas Pharma Global Development, Northbrook, IL; Cristina Ivanescu, Quintiles, Hoofddorp, the Netherlands; Brooke Esteves, Anna Berkenblit, Andrew Strahs, AVEO Oncology, Cambridge, MA; Thomas E. Hutson, Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas, TX.
J Clin Oncol. 2013 Oct 20;31(30):3791-9. doi: 10.1200/JCO.2012.47.4940. Epub 2013 Sep 9.
Tivozanib is a potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor 1 (VEGFR1), -2, and -3. This phase III trial compared tivozanib with sorafenib as initial targeted therapy in patients with metastatic renal cell carcinoma (RCC).
Patients with metastatic RCC, with a clear cell component, prior nephrectomy, measurable disease, and 0 or 1 prior therapies for metastatic RCC were randomly assigned to tivozanib or sorafenib. Prior VEGF-targeted therapy and mammalian target of rapamycin inhibitor were not permitted. The primary end point was progression-free survival (PFS) by independent review.
A total of 517 patients were randomly assigned to tivozanib (n = 260) or sorafenib (n = 257). PFS was longer with tivozanib than with sorafenib in the overall population (median, 11.9 v 9.1 months; hazard ratio [HR], 0.797; 95% CI, 0.639 to 0.993; P = .042). One hundred fifty-six patients (61%) who progressed on sorafenib crossed over to receive tivozanib. The final overall survival (OS) analysis showed a trend toward longer survival on the sorafenib arm than on the tivozanib arm (median, 29.3 v 28.8 months; HR, 1.245; 95% CI, 0.954 to 1.624; P = .105). Adverse events (AEs) more common with tivozanib than with sorafenib were hypertension (44% v 34%) and dysphonia (21% v 5%). AEs more common with sorafenib than with tivozanib were hand-foot skin reaction (54% v 14%) and diarrhea (33% v 23%).
Tivozanib demonstrated improved PFS, but not OS, and a differentiated safety profile, compared with sorafenib, as initial targeted therapy for metastatic RCC.
替沃扎尼布是一种强效和选择性的血管内皮生长因子受体 1（VEGFR1）、-2 和 -3 的酪氨酸激酶抑制剂。这项 III 期试验比较了替沃扎尼布与索拉非尼作为转移性肾细胞癌（RCC）患者的初始靶向治疗药物。
患有转移性 RCC、透明细胞成分、肾切除术、可测量疾病和 0 或 1 种转移性 RCC 既往治疗的患者，被随机分配接受替沃扎尼布或索拉非尼治疗。不允许使用既往的 VEGF 靶向治疗和哺乳动物雷帕霉素靶蛋白抑制剂。主要终点是独立审查的无进展生存期（PFS）。
共有 517 名患者被随机分配至替沃扎尼布（n = 260）或索拉非尼（n = 257）组。总体人群中，替沃扎尼布的 PFS 长于索拉非尼（中位数，11.9 个月比 9.1 个月；风险比 [HR]，0.797；95%CI，0.639 至 0.993；P =.042）。156 名（61%）在索拉非尼治疗后进展的患者交叉接受替沃扎尼布治疗。最终的总生存（OS）分析显示，索拉非尼组的生存时间长于替沃扎尼布组的趋势（中位数，29.3 个月比 28.8 个月；HR，1.245；95%CI，0.954 至 1.624；P =.105）。替沃扎尼布组比索拉非尼组更常见的不良反应（AE）是高血压（44%比 34%）和发音困难（21%比 5%）。索拉非尼组比替沃扎尼布组更常见的 AE 是手足皮肤反应（54%比 14%）和腹泻（33%比 23%）。
与索拉非尼相比，替沃扎尼布作为转移性 RCC 的初始靶向治疗药物，可改善 PFS，但不改善 OS，并具有不同的安全性特征。
