Division of Hematology Oncology, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
Clinical Development and Medical Affairs, AVEO Oncology, Boston, MA, USA.
Oncologist. 2024 Mar 4;29(3):254-262. doi: 10.1093/oncolo/oyad348.
Tivozanib is an oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) with efficacy in advanced renal cell carcinoma (RCC). Long-term exploratory analyses from the TIVO-3 trial in relapsed/refractory (R/R) RCC including patients (26%) with prior immuno-oncology (IO) therapy are reported.
Patients with R/R advanced RCC that progressed with 2 or 3 prior systemic therapies (≥1 VEGFR TKI) were randomized to tivozanib 1.5 mg QD or sorafenib 400 mg BID, stratified by IMDC risk and previous therapy. Safety, investigator-assessed long-term progression-free survival (LT-PFS), and serial overall survival (OS) were assessed.
Mean time on treatment was 11.0 months with tivozanib (n = 175) and 6.3 months with sorafenib (n = 175). Fewer grade ≥3 treatment-related adverse events occurred with tivozanib (46%) than sorafenib (55%). Dose modification rates were lower with tivozanib than sorafenib across age/prior IO subgroups; prior IO therapy did not impact dose reductions or discontinuations in either arm. Landmark LT-PFS rates were higher with tivozanib (3 years: 12.3% vs 2.4%; 4 years: 7.6% vs 0%). After 22.8 months mean follow-up, the OS HR was 0.89 (95% CI, 0.70-1.14); when conditioned on 12-month landmark PFS, tivozanib showed significant OS improvement over sorafenib (HR, 0.45; 95% CI, 0.22-0.91; 2-sided P = .0221).
Tivozanib demonstrated a consistent safety profile and long-term survival benefit in patients with R/R advanced RCC who were alive and progression free at 12 months. These post hoc exploratory analyses of LT-PFS and conditional OS support a clinically meaningful improvement with tivozanib versus sorafenib in this advanced RCC population.
替沃扎尼布是一种口服血管内皮生长因子受体（VEGFR）酪氨酸激酶抑制剂（TKI），在晚期肾细胞癌（RCC）中具有疗效。在复发/难治性（R/R）RCC 的 TIVO-3 试验中报告了包括先前接受过免疫肿瘤学（IO）治疗的患者（26%）的长期探索性分析。
接受过 2 或 3 种先前系统治疗（≥1 种 VEGFR TKI）进展的 R/R 晚期 RCC 患者按 IMDC 风险和先前治疗分层，随机接受替沃扎尼布 1.5mgQD 或索拉非尼 400mgBID。评估安全性、研究者评估的长期无进展生存期（LT-PFS）和连续总生存期（OS）。
替沃扎尼布（n=175）的中位治疗时间为 11.0 个月，索拉非尼（n=175）为 6.3 个月。替沃扎尼布（46%）发生的治疗相关不良事件≥3 级发生率低于索拉非尼（55%）。在年龄/先前 IO 亚组中，替沃扎尼布的剂量调整率低于索拉非尼；在两个治疗组中，先前的 IO 治疗都没有影响剂量的减少或停药。替沃扎尼布的 LT-PFS 里程碑率较高（3 年：12.3% vs 2.4%；4 年：7.6% vs 0%）。在平均 22.8 个月的随访后，OS 的 HR 为 0.89（95%CI，0.70-1.14）；当根据 12 个月的 LT-PFS 进行条件分析时，替沃扎尼布与索拉非尼相比 OS 显著改善（HR，0.45；95%CI，0.22-0.91；双侧 P=0.0221）。
在 12 个月时无进展且存活的 R/R 晚期 RCC 患者中，替沃扎尼布表现出一致的安全性和长期生存获益。这些 LT-PFS 和条件 OS 的事后探索性分析支持在该晚期 RCC 人群中，替沃扎尼布与索拉非尼相比具有临床意义的改善。
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