FDA Approves Tivozanib as First Therapy for a Relapsed/Refractory Advanced RCC Subgroup

The first therapy for adults with relapsed or refractory advanced renal cell carcinoma who have received two or more prior systemic therapies has been granted approval by the FDA.

The FDA has granted approval to tivozanib (Fotivda) as treatment of adults with relapsed or refractory advanced renal cell carcinoma (RCC) who have received two or more prior systemic therapies, according to a press release from AVEO Oncology. Tivozanib is the first therapy approved for this indication.1

Approval was granted to tivozanib on the basis of data from the phase 2 TIVO-3 clinical trial (NCT02627963). TIVO-3 is a controlled, multicenter, open-label, phase III trial of 350 patients with highly refractory metastatic RCC who had failed ≥2 prior regimens, including VEGF tyrosine kinase inhibitor treatment. Patients in the study were randomized 1:1 to receive either oral tivozanib or sorafenib.

In the study, tivozanib demonstrated superiority over sorafenib (Nexavar) as treatment of refractory, metastatic RCC.

“Today’s approval of Fotivda provides a new tool for treating patients with kidney cancer who have relapsed or become refractory to two or more prior systemic therapies,” said Brian Rini, MD, chief of Clinical Trials at Vanderbilt Ingram Cancer Center and principal investigator of the TIVO-3 trial, in a statement. “With advances in RCC treatment, patients are living longer, increasing the need for proven, well-tolerated treatment options in the relapsed or refractory setting.”

According to results presented during the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting, the hazard ratio for overall survival (OS) with tivozanib versus sorafenib was 0.97 (95% CI, 0.75-1.24; =.78). The median OS in the tivozanib arm was 16.4 months (95% CI, 13.4-22.2) and 19.2 months in the sorafenib arm (95% CI, 15.0-24.2). The study included a subgroup of patients who received previous checkpoint inhibitor and VEGF inhibitor therapy, and in this population, the HR for death was 0.55 and was 0.57 for those who received 2 prior checkpoint or VEGF inhibitors. Prior to the 2020 ASCO meeting update, it was reported that the median progression-free survival for tivozanib was 5.6 months versus 3.9 months for sorafenib (HR, 0.73; 95% CI, 0.56-0.94; =.016).2

In terms of response, tivozanib led to an 18% (95% CI: 12%-24%) overall response rate compared with 8% (95% CI: 4%-13%) in the sorafenib arm.

Tivozanib appeared to have a favorable safety profile during the study. Treatment-related adverse events (TRAEs) were observed in 84% compared with 94% of the sorafenib arm. Serious TRAEs were observed in 11% of the patients who received tivozanib compared with 10% of those treated with sorafenib.

Cases of fatigue, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis were the most common AE, which occurred in more than 20% of the study population. The most frequently observed grade 3 or 4 TRAEs in TIVO-3 were hypertension (38%), diarrhea (33%), fatigue (29%), and decreased appetite (27%). Notably, 48% of the tivozanib group versus 64% of the sorafenib group required dose reductions as a result of toxicity (P =.0164). Treatment discontinuation occurred in 8% of the tivozanib arm compared with 15% of the control arm.

“The TIVO-3 study is the first positive Phase 3 study in RCC patients who received two or more prior systemic therapies, and also the first Phase 3 RCC study to include a predefined population of patients who have received prior immunotherapy, the current standard of care in earlier-line treatment. With this approval, I believe Fotivda represents an attractive intervention, and expect it to play a meaningful role in the evolving RCC treatment landscape, " added Rini.1

The FDA recommends that tivozanib be dosed at 1.34 mg once daily with or without food for 21 days every 28 days on treatment followed by 7 days off treatment in a 28-day cycle, until disease progression or unacceptable toxicity.

“We believe in Fotivda potential to provide a differentiated treatment option for the growing number of individuals in the United States with relapsed or refractory RCC, and today marks the culmination of many years of hard work and determination of many individuals to bring this therapy to patients,” said Michael Bailey, president and chief executive officer of AVEO, in the press release. “With today’s approval, AVEO begins its journey as a commercial-stage company, a noteworthy accomplishment in our industry. On behalf of the entire AVEO team, I would like to thank all the patients, their families, and caregivers whose tireless efforts made this day possible.”


1. AVEO Oncology announces U.S. FDA approval of Fotivda® (tivozanib) for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma. News release. AVEO Oncology. March 10, 2021. Accessed March 10, 2021. https://bwnews.pr/3bw0FoW

2. 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.