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).
Patients with metastatic renal cell carcinoma for whom 2 or 3 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:
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.
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: The study authors' full disclosures can be found at coi.asco.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.