"We believe the TIVO-3 data demonstrate a favorable risk/benefit profile for tivozanib in the growing population of patients who have relapsed or become refractory to multiple lines of therapy, including checkpoint inhibitors."
In the phase II TIVO-3 trial, treatment with tivozanib (Fotivda) in patients with highly relapsed or refractory metastatic renal cell carcinoma (RCC) significantly improved progression-free survival (PFS) compared with sorafenib (Nexavar) and demonstrated a similar overall survival (OS), according to results presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program.1,2
Final OS hazard ratio (HR) was 0.97 (95% CI, 0.75-1.24; P = .78). An updated analysis of the data found that with a median follow-up of 38 months for tivozanib and 40 months for sorafenib, median OS was 16.4 months for tivozanib (95% CI, 13.4-22.2) and 19.2 months for sorafenib (95% CI, 15.0-24.2). A subset analysis showed the greatest benefit was derived by the cohort of patients that had received treatment with a prior checkpoint inhibitor and VEGF inhibitor, with an HR of 0.55, or 2 VEGF TKIs, with an HR of 0.57.
Previously released data showed an increased median PFS for tivozanib when compared with sorafenib, (5.6 months vs 3.9 months; HR, 0.73; 95% CI, 0.56-0.94; P = .016).
“We believe the TIVO-3 data demonstrate a favorable risk/benefit profile for tivozanib in the growing population of patients who have relapsed or become refractory to multiple lines of therapy, including checkpoint inhibitors,” Sumanta Pal, MD, associate clinical professor, Department of Medical Oncology and Therapeutics Research, and co-director, Kidney Cancer Program, at City of Hope Comprehensive Cancer Center, said in a press release.2
“The lack of clinical data to guide treatment decisions in a robust, evidence-based manner in this setting is a serious and growing unmet medical need, particularly as this population continues to grow thanks to improved treatment in earlier lines,” he added. “TIVO-3 provides the first positive superiority study to help guide this important treatment decision and, furthermore, offers this highly refractory patient population a favorable tolerability profile as indicated by fewer dose reductions, interruptions and discontinuations over a less selective VEGFR TKI in sorafenib.”
The TIVO-3 study was a controlled, multicenter, open-label, phase III trial which randomized 350 patients with highly refractory metastatic RCC who had failed ≥2 prior regimens, including VEGF-TKI treatment, 1:1 to receive either oral tivozanib or sorafenib. Crossover between arms was not permitted.
Eighteen percent (n = 31) of patients in the tivozanib arm achieved partial response, compared with 8% (n = 14) of those in the sorafenib arm. The objective response rate was 34% for tivozanib versus 24% for sorafenib.
Treatment with tivozanib was found to be generally well-tolerated, and the safety profile was favorable when compared with sorafenib. Treatment-related adverse events (TRAEs) were reported in 84% (n = 146) of patients receiving tivozanib and 94% (n = 160) of those receiving sorafenib. Serious TRAEs occurred in 11% (n = 19) of patients treated with tivozanib versus 10% (n = 17) of patients who received sorafenib.
The most common grade 3 or 4 AE reported in patients receiving tivozanib and sorafenib was hypertension (21% vs 14%, respectively). The most commonly reported any grade AEs associated with tivozanib were hypertension (38%), diarrhea (33%), fatigue (29%), and decreased appetite (27%).
The investigators reported significantly reduced dose reductions and interruptions due to AEs for tivozanib versus sorafenib (48% vs 63%; P = .0164), despite nearly double the average time of cycles initiated for the tivozanib arm (11.9 months vs 6.7 months, respectively). Treatment related AEs leading to permanent discontinuation were 8% for tivozanib compared with 15% for sorafenib.
1. Pal SK, Escudier B, Atkins MB, et al. TIVO-3: Final OS analysis of a phase III, randomized, controlled, multicenter, open-label study to compare tivozanib to sorafenib in subjects with metastatic renal cell carcinoma (RCC). Presented at: 2020 ASCO Virtual Program; May 27, 2020. Abstract 5062
2. AVEO Oncology Announces TIVO-3 Final Overall Survival Results Featured at ASCO 2020 Virtual Scientific Program and Submitted to U.S. FDA as Part of NDA Filing. News release. AVEO Oncology. May 29, 2020. Accessed May 29, 2020. https://bit.ly/2ZO078v.