ASCO GU 2021: TIVO-3: Tivozanib in Patients with Advanced Renal Cell Carcinoma Who Have Progressed After Treatment with Axitinib

( Tivozanib is a potent and highly selective VEGF receptor tyrosine kinase inhibitor in clinical development for renal cell carcinoma (RCC). Axitinib is also a potent and selective VEGF-receptor inhibitor now commonly part of front-line advanced RCC treatment. In the TIVO-3 trial, tivozanib demonstrated significantly greater progression-free survival (PFS) (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.56-0.94) and objective response rate (ORR) (15.2% versus 7.5%, p=0.003) versus sorafenib in the intention to treat population, in the subset of patients treated with two prior VEGFR-tyrosine kinase inhibitors (TKI), and in patients treated with a prior VEGFR-TKI and an anti-PD-1 antibody.1 The activity of tivozanib after axitinib has not been previously defined, and as such the activity of tivozanib after prior therapy types including axitinib is of clinical relevance. At the 2021 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium, Dr. Brian Rini and colleagues presented results of the TIVO-3 trial testing tivozanib in patients with advanced RCC who had progressed after prior axitinib treatment.

The pivotal TIVO-3 study enrolled subjects with metastatic renal cell carcinoma (mRCC) who failed two or three prior systemic regimens, one of which included a VEGFR-TKI, stratified by the International Metastatic RCC Database Consortium (IMDC) risk category and type of prior therapy (two TKIs; TKI plus checkpoint inhibitor; TKI plus other) then randomized patients in a 1:1 ratio to tivozanib or sorafenib. The study design of TIVO-3 is as follows:

tivo 3 phase 3 randmozed trial to compare tivozanib to sorafenib in subjects with rcc

The primary objective of the overall trial was to compare progression-free survival by blinded independent radiological review. Patients with prior axitinib received as monotherapy in the second or third-line setting and other predefined subgroups were reviewed for the outcome with tivozanib in the current analysis.

There were 172 patients with prior axitinib treatment and 178 patients with no prior axitinib treatment. Patients treated with tivozanib after prior axitinib had a progression-free survival of 5.5 months and an ORR of 13% compared to 3.7 months and 8% for patients treated with sunitinib. A tabular summary of the results are as follows:

tivo 3 summary of results

Treatment-related adverse events were comparable between these two cohorts.

Dr. Rini concluded this presentation of the TIVO-3 trial assessing tivozanib in patients after previous axitinib with the following take-home messages:

  • Tivozanib is active in patients previously treated with axitinib, a similarly potent and selective VEGFR-TKI
  • Prior treatment with axitinib does not influence the tolerability of tivozanib in third- and fourth-line patients
  • These results suggest that a selective VEGFR inhibitor, tivozanib, is active after prior axitinib and provides superior benefit compared to the multi-targeted VEGFR-TKI sorafenib
Presented by: Brian I. Rini, MD, Professor of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee

Written by: Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Augusta, Georgia, Twitter: @zklaassen_md during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021


1. Rini, Brian I., Sumanta K. Pal, Bernard J. Escudier, Michael B. Atkins, Thomas E. Hutson, Camillo Porta, Elena Verzoni, Michael N. Needle, and David F. McDermott. "Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3): a phase 3, multicentre, randomised, controlled, open-label study." The Lancet Oncology 21, no. 1 (2020): 95-104.