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

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