Related Experiment Video
Updated: Nov 5, 2025

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Q-TWiST Analysis of Tivozanib Versus Sorafenib in Patients With Advanced Renal Cell Carcinoma in the TIVO-3 Study
Michael Szarek1, Michael N Needle2, Brian I Rini3
1CPC Clinical Research and Department of Medicine, Division of Cardiovascular Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO; SUNY Downstate Medical Center, Brooklyn, NY.
Background:
In TIVO-3, tivozanib increased progression-free survival with no difference in overall survival relative to sorafenib as third- or fourth-line therapy in patients with metastatic renal cell carcinoma. We applied quality-adjusted time without symptoms of disease and toxicity (Q-TWiST) methods to quantify the net health benefits of tivozanib, in the presence of similar survival, when compared with sorafenib.
Methods:
The mean Q-TWiST was calculated by applying utility coefficients of 0.5, 1.0, and 0.5 to the 36-month restricted mean health states of time with toxicity (TOX), TWiST, and time after progression/relapse, respectively. The relative Q-TWiST gain was defined as the mean absolute Q-TWiST difference divided by the sorafenib mean overall survival.
Results:
The mean TWiST was longer for tivozanib than for sorafenib, mean time after progression/relapse was shorter for tivozanib, with no difference in mean TOX. Mean Q-TWiST was 15.04 months and 12.78 months for tivozanib and sorafenib, respectively (P = .0493). The tivozanib relative gain was 11.2%.
Discussion:
Tivozanib increased Q-TWiST relative to sorafenib, primarily through an increase in TWiST, which is generally considered to be the highest utility state.
Conclusion:
Q-TWiST may be considered an alternative patient-centered measure of benefit of tivozanib in as a third- or fourth-line therapy in patients with renal cell carcinoma.
Clinical Trial Information:
NCT02627963.
Related Concept Videos
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Treatment Resistant Cancers
Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Cancer Survival Analysis
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...

