2. UroToday Home
  3. Recent Abstracts
  4. Urologic Oncology
  5. Renal Cancer

AVEO Oncology Announces Publication of Long-Term Survival in Patients With Relapsed/Refractory Advanced Renal Cell Carcinoma Treated With Tivozanib: Analysis of the Phase III TIVO-3 Trial in The Oncologist

Reno, Nevada (UroToday.com) -- AVEO Oncology, an LG Chem company (“AVEO”), today announced The Oncologist has published a post-hoc analysis of long-term progression free survival, overall survival and safety data from the Phase 3 TIVO-3 trial evaluating FOTIVDA® (tivozanib) in patients with relapsed or refractory (R/R) advanced renal cell carcinoma (RCC). In the publication, FOTIVDA demonstrated a consistent safety profile and a long-term survival benefit in patients who were alive and progression-free at 12 months, suggesting a durable clinical benefit and safety across age groups regardless of prior treatment.

“The post-hoc analysis from TIVO-3 provides additional evidence supporting the clinical utility of tivozanib in the third- or fourth-line refractory setting in patients with advanced renal cell carcinoma,” said lead author Kathryn E. Beckermann, MD, PhD, Assistant Professor of Medicine in the Division of Hematology Oncology at Vanderbilt-Ingram Cancer Center. “The results suggest there is a clinically meaningful population of patients who can experience a long-term survival benefit from tivozanib over sorafenib.”
TIVO-3 compared the efficacy and safety of the vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) FOTIVDA and sorafenib (Nexavar®) in patients with R/R advanced RCC whose disease progressed with two or three prior systemic therapies. The trial included a predefined subgroup of patients (26%) who were previously treated with both an immuno-oncology (IO) therapy and a VEGFR TKI.

The post hoc analysis showed investigator-assessed landmark long-term progression-free survival (PFS) rates were higher with FOTIVDA compared to sorafenib (3 years: 12.3% vs. 2.4%; 4 years: 7.6% vs. 0%). After 22.8 months mean follow-up, the overall survival (OS) hazard ratio (HR) for FOTIVDA was 0.89 (95% confidence interval [CI]: 0.70-1.14); when conditioned on a clinically meaningful 12-month PFS time point, FOTIVDA showed significant improvement in OS compared to sorafenib (HR: 0.45; 95% CI: 0.22-0.91; 2-sided P = 0.0221). Mean time on treatment was 11.0 months with FOTIVDA and 6.3 months with sorafenib. There were fewer treatment-related adverse events (TRAEs) and lower dose modification rates with FOTIVDA than with sorafenib as well as fewer grade ≥3 TRAEs on FOTIVDA (46%) than sorafenib (55%). Dose modification rates were lower with FOTIVDA than with sorafenib across age and prior IO subgroups; and prior IO therapy did not impact dose reductions or discontinuations in either arm.

The advent of targeted therapies and IO therapies is considered a major advancement in the treatment of RCC, and IO-based combination therapy is the frontline standard of care for patients with advanced RCC who require systemic therapy.4 However, despite the demonstrated benefits of IO combination therapies, most patients with RCC ultimately experience disease progression and require subsequent treatments,5 underscoring the need for safe, tolerable and effective therapies in the refractory setting.

“For patients with relapsed or refractory advanced renal cell carcinoma, long-term progression-free survival is a vital measure of the value of anticancer therapy,” commented Michael Bailey, President and CEO of AVEO Oncology. “The long term PFS analysis combined with the post hoc conditional survival analysis is especially encouraging in this highly refractory population, as it builds upon the previously reported PFS advantage for FOTIVDA over sorafenib, a non-selective VEGFR TKI.”
Study Details

TIVO-3 was a Phase 3, global, open-label, parallel-arm study comparing the safety and efficacy of FOTIVDA versus sorafenib in patients with R/R advanced RCC whose disease progressed with two or three prior VEGFR TKI systemic regimens. The trial randomized 350 patients to receive FOTIVDA (1.5 mg once daily) or sorafenib (400 mg twice daily). The intent-to-treat (ITT) population included 175 patients in each arm; the safety population included 173 patients in the FOTIVDA arm and 170 in the sorafenib arm.

References
  1. American Cancer Society. Cancer Facts & Figures 2024. Atlanta: American Cancer Society; 2024. https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/2024-cancer-factsfigures.html.
  2. Tran J. Ornstein MC. Clinical review on the management of metastatic renal cell carcinoma. JCO Oncol Pract. 2021;18(3):187-196. https://ascopubs.org/doi/10.1200/OP.21.00419.
  3. Bergstrom A, Hsieh CC, Lindblad P, et al. Obesity and renal cell cancer – a quantitative review. Br J Cancer. 2001;85(7):984-990. https://www.nature.com/articles/6692040.
  4. Tenold M, Ravi P, Kumar M, et al. Current approaches to the treatment of advanced or metastatic renal cell carcinoma. Am Soc Clin Oncol Educ Book. 2020;40:1-10. https://ascopubs.org/doi/10.1200/EDBK_279881.
  5. Vento JA, Rini BI. Treatment of refractory metastatic renal cell carcinoma. Cancers (Basel). 2022;14(20):5005. doi: 10.3390/cancers14205005.
Source: AVEO Pharmaceuticals, Inc. (2024). AVEO Oncology Announces Publication of Long-Term Survival in Patients With Relapsed/Refractory Advanced Renal Cell Carcinoma Treated With Tivozanib: Analysis of the Phase III TIVO-3 Trial in The Oncologist [Press release]. https://www.aveooncology.com/aveo-oncology-announces-publication-of-long-term-survivalin-patients-with-relapsed-refractory-advanced-renal-cellcarcinoma-treated-with-tivozanib-analysis-of-the-phase-iiitivo-3-trial-in-the-oncologi/.