The renal cell carcinoma (RCC) drug tivozanib (Fotivda) is now commercially available in the United States, according to AVEO Oncology, the developer of the VEGF tyrosine kinase inhibitor (TKI).1
The FDA approved tivozanib on March 10, 2021,2 for the treatment of adult patients with relapsed or refractory advanced RCC who have received 2 or more prior systemic therapies, based on data from the phase 3 TIVO-3 trial.
Results from TIVO-3 presented during the 2020 ASCO Virtual Scientific Program3 showed that treatment with tivozanib led to a significant improvement in progression-free survival (PFS) compared with sorafenib (Nexavar), with similar overall survival (OS), in patients with relapsed/refractory metastatic RCC.
The findings showed that the final hazard ratio (HR) for OS was 0.97 (P = .78). Moreover, an updated analysis of the data found that, with a median follow-up of 38 months for tivozanib and 40 months for sorafenib, the median OS was 16.4 months for tivozanib and 19.2 months for sorafenib. A subset analysis showed the greatest benefit was derived by the cohort of patients who previously received a checkpoint inhibitor and VEGF inhibitor, with an HR of 0.55, or 2 VEGF TKIs, with an HR of 0.57.
Prior findings showed an increased median PFS for tivozanib when compared with sorafenib at 5.6 months versus 3.9 months, respectively (HR, 0.73; P = .016).
“We are keenly focused on ensuring that Fotivda is available to as many appropriate patients as possible,” Mike Ferraresso, chief commercial officer of AVEO, stated in a press release. “As part of this effort and our commitment to the RCC community, we have put in place an assistance program, AVEO ACE, which we believe will optimize patient access and help patients navigate their treatment journey. With the early FDA approval, the team has worked hard to make Fotivda available to patients as quickly as possible through our distribution partners and we believe we are well positioned for the successful launch of Fotivda.
In the multicenter, open-label, randomized TIVO-3 trial, 350 patients were split evenly between the 2 drugs and stratified by International Metastatic Renal Cell Carcinoma Database Consortium risk category and type of previous therapy.2 These patients had to progress on 2 or 3 prior systemic regimens, at least 1 of which had to be a VEGFR tyrosine kinase inhibitor other than sorafenib or tivozanib.
Patients either received 1.5 mg of tivozanib mg orally once a day on 4-week cycles or sorafenib at 400 mg orally twice a day continuously. The primary end point was PFS by independent review in the intention-to-treat population.
The most common grade 3/4 treatment-related adverse events (TRAEs) in the originally published data were hypertension in 20% of patients receiving tivozanib and 14% of patients receiving sorafenib. Serious TRAEs were observed in 11% versus 10% of patients respectively, but no treatment-related deaths were reported.
Tivozanib is now being explored in ongoing combination trials. For example, the phase 3 TiNivo-2 trial is exploring the VEGF-TKI in combination with the PD-1 inhibitor nivolumab (Opdivo) in patients with relapsed/refractory RCC.4
1. AVEO Oncology Announces U.S. Commercial Availability of FOTIVDA® (tivozanib) for the Treatment of Adult Patients With Relapsed or Refractory Advanced Renal Cell Carcinoma Ahead of Previous Guidance. Published online March 22, 2021. Accessed March 22, 2021. https://bit.ly/3cc5KTu.
2. AVEO Oncology Announces U.S. FDA Approval of FOTIVDA® (tivozanib) for the Treatment of Adult Patients with Relapsed or Refractory Advanced Renal Cell Carcinoma. Published online March 10, 2021. Accessed March 10, 2021. https://bwnews.pr/3vbdRY4.
3. 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.
4. AVEO Oncology Announces Collaboration with Bristol Myers Squibb to Evaluate FOTIVDA® (tivozanib) in Combination with OPDIVO® (nivolumab) in Pivotal Phase 3 TiNivo-2 Trial in IO Relapsed Renal Cell Carcinoma. Posted online March 12, 2021. Accessed March 12, 2021. https://bit.ly/3ldIasp.