Q-TWiST Analysis of Tivozanib Versus Sorafenib in Patients With Advanced Renal Cell Carcinoma in the TIVO-3 Study

Abstract

In TIVO-3, tivozanib increased progression-free survival relative to sorafenib in patients with metastatic renal cell carcinoma. In the current analysis, tivozanib also increased quality-adjusted time without symptoms of disease and toxicity (Q-TWiST). As an outcome that integrates the quantity and quality of survival, Q-TWiST may be considered an alternative patient-centered measure of tivozanib benefit in renal cell carcinoma. 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, pr imar ily 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

Adjuvant Therapy for High-Risk Localized Renal Cell Carcinoma: Current Landscape and Future Direction

“…There remain a number of guideline-directed agents utilized for mRCC that have not yet been studied in the adjuvant setting for patients with locally or regionally advanced RCC at high risk of recurrence. 86 Some of these regimens include single agents, such as cabozantinib, 91–95 temsirolimus, 96 tivozanib, 97 , 98 bevacizumab, 99 and belzutifan (phase III trial is ongoing). 30 , 100 , 101 Furthermore, a number of combined agent regimens have proven beneficial in mRCC, without trials to either support or contraindicate their adjuvant use in patients with high-risk RCC.…”

Design, synthesis, docking, ADMET studies, and anticancer evaluation of new 3-methylquinoxaline derivatives as VEGFR-2 inhibitors and apoptosis inducers

“…Regorafenib 4, a fluoro derivative of sorafenib, has been developed to inhibits VEGFR1-3 25 . Tivozanib 5, a VEGFR-2 inhibitor, has been approved by the FDA in March 2021 for the treatment of RCC [26][27][28] . Sunitinib 1 is a VEGFR-2 kinase inhibitor that was approved for the treatment of RCC and of gastrointestinal stromal tumours (GIST) 29 .…”