The TIVO-3 trial was conducted to confirm progression-free survival results from the TIVO-1 trial, which found an improvement in median progression-free survival in patients with metastatic renal cell carcinoma treated with tivozanib vs sorafenib. Findings from TIVO-3 were presented by Rini et al at the 2019 Genitourinary Cancers Symposium (Abstract 541).1
Methods
Patients with metastatic renal cell carcinoma for whom two or three prior regimens had failed were stratified by independent data monitoring committee risk category and type of prior therapy—either two tyrosine kinase inhibitors, a tyrosine kinase inhibitor plus a checkpoint inhibitor, or a tyrosine kinase inhibitor plus another treatment. Patients were then randomly assigned 1:1 to receive either tivozanib or sorafenib.
A total of 350 patients were enrolled to yield 244 events with ~88% power to detect a difference of 6 months vs 4 months, with a two-sided P value of .05 by the log-rank test. The tivozanib group and the sorafenib group were well balanced for demographics and prior cancer history:
- 60% of subjects had received 2 prior lines of therapy
- 40% of subjects had received 3 prior lines of therapy
- 28% had received prior treatment with a checkpoint inhibitor.
The primary objective of TIVO-3 was to compare progression-free survival by blinded radiologic review. Secondary trial endpoints were overall survival, safety, objective response rate, and duration of response.
Results
Patients treated with tivozanib demonstrated an improvement in median progression-free survival compared to sorafenib—5.6 vs 3.9 months. The progression-free survival rate at 2 years was 18% for patients treated with tivozanib and 5% for patients treated with sorafenib, and the overall response rate was 18% for tivozanib compared to 8% for sorafenib.
In terms of safety, 44% of patients treated with tivozanib experienced a grade 3 treatment-related adverse event compared to 55% of patients treated with sorafenib. Patients in the tivozanib-treated group were less likely to require a dose reduction, dose interruption, or dose discontinuation.
Overall survival favored sorafenib in the TIVO-1 trial, which the investigators speculated was likely due to an imbalanced crossover to active treatments. An interim analysis of overall survival in TIVO-3 also showed no benefit with tivozanib, but a definitive analysis of more mature survival results is planned for later this year.
DISCLOSURE: Dr. Rini has served in a consulting or advisory role with Bristol-Myers Squibb, Merck, Novartis, Pfizer, Roche/Genentech, and Synthorx. His institution has received research funding from AstraZeneca/MedImmune, Bristol-Myers Squibb, Merck, Peloton Therapeutics, Pfizer, and Roche/Genentech. Dr. Rini has received payment for travel, accommodations, and expenses from Bristol-Myers Squibb, Merck, and Pfizer. For complete disclosure information for all study authors, visit https://coi.asco.org/Report/ViewAbstractCOI?id=242305.
REFERENCE
1. Rini BI, Pal SK, Escudier B, et al: TIVO-3: A phase III, randomized, controlled, multicenter, open-label study to compare tivozanib to sorafenib in subjects with refractory advanced renal cell carcinoma. 2019 Genitourinary Cancers Symposium. Abstract 541. Presented February 16, 2019.
