Tivozanib Improves OS in Long-Term Responders in Relapsed/Refractory, Advanced RCC

Tivozanib (Fotivda) demonstrated an improvement in overall survival (OS) compared with sorafenib (Nexavar) in pretreated patients with advanced clear cell renal cell carcinoma (RCC), particularly in those who remained progression-free at 1 year and beyond, according to long-term findings from the phase 3 TIVO-3 trial (NCT02627963) presented at the 2022 Kidney Cancer Research Summit.

At 2 years following the last-patient-in, the mean follow-up was 17.9 months (95% CI, 16.7-19.1), and 65% (n = 227) of patients had experienced an OS event. At that time, the OS hazard ratio (HR) was 0.99 (95% CI, 0.76-1.29). With mean follow-up extended to 22.8 months (95% CI, 20.9-24.6), 80% (n = 280) of patients had experienced an OS event, and the OS HR lowered to 0.89 (95% CI, 0.70-1.14; P = .3533). Here, the median OS was 16.4 months (95% CI, 13.4-21.9) with tivozanib vs 19.1 months (95% CI, 14.9-24.2) with sorafenib.

“Long-term follow-up in TIVO-3 suggests that early and consistent PFS [progression-free survival] benefit with tivozanib over sorafenib may be associated with an improvement in OS HR over time as more events accumulate,” lead study author Brian I. Rini, MD, professor of medicine at Vanderbilt University Medical Center in Nashville, Tennessee, and coauthors, wrote in the poster.

Tivozanib is an oral VEGF inhibitor approved by the FDA for the treatment of patients with relapsed/refractory RCC following at least 2 prior therapies.

The approval was based on prior findings from TIVO-3, which demonstrated a significant improvement in PFS with tivozanib vs sorafenib (HR, 0.73; 95% CI, 0.56-0.93). Additional findings showed that the 3-year PFS rate favored tivozanib vs sorafenib, at 12% vs 2%, respectively.

The study enrolled 350 patients who had progressed on 2 or 3 prior systemic treatments, including at least 1 VEGFR TKI. Patients were randomly assigned 1:1 to 1.34 mg of oral tivozanib daily for 3 weeks on, 1 week off, or 400 mg of oral sorafenib twice daily every 4 weeks until progression or unacceptable toxicity.

To better gauge survival data, investigators evaluated the effects of event accumulation and data maturation on the stability of Kaplan-Meier survival estimates over time with extended follow-up. 

“Serial OS analyses using Kaplan-Meier estimates are affected by increased curve reliability with decreased censoring and limited residual patients at risk for death,” the study authors wrote.

Notably, when OS was conditioned on clinically relevant landmark PFS time points, a statistically significant improvement in OS was seen in patients who received tivozanib vs sorafenib (12-month PFS: HR, 0.45; 95% CI, 0.22-0.91; P = .0221; 18-month PFS: HR, 0.46; 95% CI, 0.15-1.39; P = .1617).

When conditioned on PFS of at least 12 months, the median OS was 48.3 months (95% CI, 32.8–not reached [NR]) with tivozanib vs 32.8 months (95% CI, 27.6-50.0) with sorafenib. When conditioned on PFS of at least 18 months, the median OS was 54.3 months (95% CI, 44.9-NR) and 50.0 months (95% CI, 32.4-NR) with tivozanib and sorafenib, respectively.

Reference

Rini BI, Pal SK, Escudier B, et al. Maturation of overall survival in TIVO-3 with long-term follow-up. Presented at: Kidney Cancer Research Summit; October 6-7, 2022; Philadelphia, PA. Abstract 75. Accessed October 10, 2022. https://bit.ly/3RJn7wE