Michael Szarek, PhD, on the Outcomes of a Q-TWiST Analysis From the Phase 3 TIVO-3 Study

February 27, 2021
Michael Szarek, PhD

An analysis revealed that as a third- or fourth-line treatment for RCC, tivozanib significantly increased Q-TWiST compared with sorafenib, primarily through an increase in TWiST.

Results of an analysis of tivozanib (Fotivda) versus sorafenib (Nexavar) in patients with advanced renal cell carcinoma (RCC) included in the phase 3 TIVO-3 study (NCT02627963), which were presented at the American Society of Clinical Oncology (ASCO) 2021 Genitourinary Cancers Symposium, suggest Q-TWiST may be considered an alternative patient-centered measure of benefit in these settings.

The analysis revealed that as a third- or fourth-line treatment for RCC, tivozanib significantly increased Q-TWiST compared with sorafenib, primarily through an increase in TWiST.

In an interview with CancerNetwork®, Michael Szarek, PhD, of the SUNY Downstate Medical Center, explained this observed outcome and why it is so significant for patients with advanced RCC.

Transcript:

You take a patient’s survival time, and you divide it into 3 mutually exclusive states. [Toxicity] time, which is the time that patients experience toxicity prior to progression; in our case, we defined that as grade 3 or 4 adverse events. Then there’s TWiST time, which is the time prior to progression where the patient is not experiencing that toxicity. Then there’s time after progression [or relapse], which is called REL time. And what we found is that by splitting every patient’s survival into those 3 states, tivozanib increased TWiST time; there was really no difference in [toxicity] time. And because of the similar survival between the 2 treatment groups, REL time was longer for sorafenib than for tivozanib. However, part of the Q-TWiST analysis is that you apply weight to each state, and the idea is that TWiST time is more valuable to a patient than REL time or [toxicity] time, which makes sense because that’s the ideal situation where prior to progression, you’re not experiencing any toxicity. And so, when you apply weight to those 3 states, we found a significant benefit of tivozanib relative to sorafenib on Q-TWiST. It’s, in a sense, confirmed the progression-free survival results of the trial in extending it by showing that if you weigh the patient survival by different quality states you also see a benefit.

References:

Szarek M, Needle MN, Rini BI, et al. Q-TWiST analysis of tivozanib (T) versus sorafenib (S) in patients with advanced renal cell carcinoma (RCC) in the TIVO-3 study. J Clin Oncol. 2021;39(suppl 6):298. doi: 10.1200/JCO.2021.39.6_suppl.298