Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA.
Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, MA.
Clin Genitourin Cancer. 2022 Dec;20(6):553-557. doi: 10.1016/j.clgc.2022.08.005. Epub 2022 Aug 23.
Tivozanib, vascular endothelial growth factor receptor inhibitor, met the primary endpoint of improved progression free survival compared to sorafenib in the phase 3 TIVO-3 study in patients with previously treated metastatic renal cell carcinoma. In this study we sought to understand the temporal characteristics of treatment related adverse events (TRAEs) and frequency and timing of the dose modifications.
In this open label, randomized, phase 3 TIVO-3 study, previously treated patients with a diagnosis of metastatic renal cell carcinoma and with measurable disease were included. Patients were randomized to receive either tivozanib 1.5 mg orally once daily in 4-week cycles or sorafenib 400 mg orally twice daily continuously. Based on updated safety analysis data (cutoff date of August 15, 2019), time to onset of the most commonly reported TRAEs, duration of toxicity, rate of dose modifications was calculated for each treatment arm.
Overall, 350 patients were randomly assigned to receive tivozanib or sorafenib;173 patients from the tivozanib arm and 170 patients from the sorafenib arm were included in this analysis. Patients received a median of 11.9 cycles (336 days) and 6.7 cycles (192 days) of tivozanib and sorafenib, respectively. Dose reductions, interruptions and treatment discontinuations were 25%, 50%, and 21%, and 39%, 50%, and 30% in the tivozanib and sorafenib arms, respectively, with a longer time to onset of TRAEs in the tivozanib arm.
Tivozanib was associated with less TRAEs, fewer dose modifications, a longer time to onset and a shorter duration of TRAEs compared to sorafenib.
在先前接受过治疗的转移性肾细胞癌患者中，与索拉非尼相比，血管内皮生长因子受体抑制剂替沃扎尼在 3 期 TIVO-3 研究中达到了改善无进展生存期的主要终点。在这项研究中，我们试图了解治疗相关不良事件（TRAEs）的时间特征，以及剂量调整的频率和时间。
在这项开放标签、随机、3 期 TIVO-3 研究中，纳入了先前诊断为转移性肾细胞癌且有可测量疾病的患者。患者被随机分配接受替沃扎尼 1.5 毫克口服，每日一次，4 周为一个周期，或索拉非尼 400 毫克口服，每日两次，连续服用。根据更新的安全性分析数据（截止日期为 2019 年 8 月 15 日），计算了每一种治疗药物的最常见报告 TRAEs 的发病时间、毒性持续时间和剂量调整率。
总体而言，350 名患者被随机分配接受替沃扎尼或索拉非尼治疗；替沃扎尼组 173 名患者和索拉非尼组 170 名患者纳入本分析。患者分别接受了中位数为 11.9 个周期（336 天）和 6.7 个周期（192 天）的替沃扎尼和索拉非尼治疗。替沃扎尼组和索拉非尼组的剂量减少、中断和治疗终止分别为 25%、50%和 21%，39%、50%和 30%，替沃扎尼组 TRAEs 的发病时间更长。
与索拉非尼相比，替沃扎尼治疗相关不良事件更少，剂量调整更少，发病时间更长，不良事件持续时间更短。
