- Christoph Baker
Mar 29 | 2021
National Comprehensive Cancer Network (NCCN) has updated its Clinical Practice Guidelines to include FOTIVDA® (tivozanib) as a recommended regimen for third- or fourth- line therapy in patients with clear cell renal cell carcinoma.
National Comprehensive Cancer Network (NCCN) has updated its Clinical Practice Guidelines to include FOTIVDA® (tivozanib) as a recommended regimen for third- or fourth- line therapy. The subsequent therapy category follows the first-line treatment regimen recommendations for patients with clear cell histology renal cell carcinoma (ccRCC)), according to AVEO Oncology, the developer of the oral, next-generation VEGF tyrosine kinase inhibitor – FOTIVDA.1
US FDA approval of tivozanib on March 10, 20212 in the relapsed/ refractory RCC setting based on data from phase 3 TIVO-3 trial, the FDA approved tivozanib 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.
On the heels of the recent TIVO-3 results presented during the 2020 ASCO Virtual Scientific Program3 which demonstrated treatment with tivozanib led to a significant improvement in progression-free survival (PFS) compared with sorafenib (Nexavar), US FDA approval of tivozanib on March 10, 20212 in the relapsed/ refractory RCC setting
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).
“Fotivda’s addition to the NCCN Guidelines provides further validation for its potential to serve as an important evidence-based, well tolerated treatment option for patients with relapsed or refractory advanced RCC. As previously announced, launch efforts are now underway, and we are committed to bringing this promising therapy to as many appropriate patients as possible.” Michael Bailey, president and chief executive officer of AVEO, stated in a press release.
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.3 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 investigated in combination with the PD-1 inhibitor nivolumab (Opdivo) in the phase 3 TiNivo-2 trial in patients with relapsed/refractory RCC .4
BACKGROUND INFORMATION:
The NCCN Clinical Practice Guidelines are the recognized standard for clinical policy in cancer care and are developed through review of evidence and recommendations from physicians and oncology researchers. The current NCCN RCC guidelines categorically make treatment recommendations for first-line or subsequent therapy options for RCC patients. FOTIVDA is now recommended by the NCCN Guidelines as a subsequent therapy for patients with ccRCC who have received two or more prior systemic therapies (Category 2a). FOTIVDA’s addition to the NCCN Guidelines follows its recent U.S. FDA approval, which was based on AVEO’s pivotal Phase 3 study, TIVO-3, comparing FOTIVDA to sorafenib in relapsed or refractory advanced RCC following two or more prior systemic therapies. The approval was also supported by three additional trials in RCC and included safety data from over 1,000 clinical trial subjects.
About FOTIVDA® (tivozanib)
FOTIVDA® (tivozanib) is an oral, next-generation vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). It is a potent, selective inhibitor of VEGFRs 1, 2, and 3 with a long half-life designed to improve efficacy and tolerability. AVEO received U.S. Food and Drug Administration (FDA) approval for FOTIVDA on March 10, 2021 for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. FOTIVDA was approved in August 2017 in the European Union and other countries in the territory of its partner EUSA Pharma (UK) Limited for the treatment of adult patients with advanced RCC. FOTIVDA was discovered by Kyowa Kirin.
INDICATIONS
FOTIVDA is indicated for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies.
References
1. AVEO Oncology Announces Addition of FOTIVDA® (tivozanib) into National Comprehensive Cancer Network Clinical Practice Guidelines. Published online March 29, 2021. Accessed March 29, 2021. https://bwnews.pr/3w9zecY.
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