Tivozanib Induces Durable Response Among Patients with Advanced Renal Cell Carcinoma

Trials designed to evaluate tivozanib (Fotivda) demonstrated durable responses, which could be key for patients being treated for relapsed or refractory renal call carcinoma (RCC), according to Brian Rini, MD, from Vanderbilt-Ingram Cancer Center.

“The biggest advantage to tivozanib is tolerability,” Rini said. “One thing where my mindset has changed now that we have immune therapy combinations that can be curative, is that when we are using single agent TKIs, we’re really just trying to control disease. Because we’re not curing those patients, and they can be on (TKI therapy) for many months or years, tolerability is really the key thing.”

In the phase III TIVO-3 trial of tivozanib versus sorafenib (Sutent) in patients who had received 2 or 3 prior lines of therapy showed a statistically significant improvement in median PFS compared with sorafenib, at 5.6 months versus 3.9 months, respectively.

In addition, 2-year PFS rates were 18% versus 5% in favor of tivozanib, and response rates were higher. The agent also induced durable responses with favorable tolerability.

CancerNetwork spoke with Rini about the durable responses associated with tivozanib, and how this could support its use in combination with checkpoint inhibitors moving forward.

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If you look at the progression-free survival curve, you do see somewhat of a tail of the curve in the tivozanib arm, which is not what we usually expect for a VEGF TKI. It may be a little premature to say that, obviously that require a longer follow-up. We don’t quite have that in this trial. But there is clearly a difference in long-term responders with tivozanib versus sorafenib. Again, a subset of patients will be exquisitely sensitive to VEGF therapy and will have long-term progression-free and overall survival, and that is why tolerability is important. One of the things that stood out to me when I saw this data was the tail of the curve. We’ll see what happens over time, of course.

Combinability really gets back to tolerability. As you well know, we’re combining VEGF agents with immune therapy – it’s standard of care in kidney cancer, a regimen like pembrolizumab (Keytruda)/axitinib (Inlyta). And there are other combinations coming. My personal belief is that all of those VEGF plus immunotherapy combinations, assuming that the immunotherapy is a PD-1, not a PD-L1, will have very similar activity. As we start to build two-drug regimens, presumably three-drug regimens, tolerability is really important. So, drugs like tivozanib, axitinib, which is also very well tolerated, are going to be the best partners.