By Dr. Bradley McGregor | Published April 02, 2025
Renal cell cancer (RCC) treatment continues to evolve, and Tivozanib (TIVO) is at the forefront of this progress. In a recent analysis, I explored the efficacy and safety exposure-response (ER) of Tivozanib, shedding light on its role as a tyrosine kinase inhibitor (TKI) in RCC management. Here’s what we found—and why it matters for patients and clinicians alike.
Building on a Strong Foundation
Our analysis didn’t start from scratch. We leveraged pharmacokinetic (PK) models from prior trials, like TIVO-3, which evaluated Tivozanib as a monotherapy. This foundation allowed us to dive deeper when designing subsequent studies, such as TIVO-2, where a critical question emerged: What’s the effect of nivolumab (Navolaab) on Tivozanib, particularly regarding hypertension?
Spoiler alert: this wasn’t about pinpointing the “most effective” concentration. Instead, it revealed something more practical—concentrations of Tivozanib are dose-dependent. Higher doses lead to higher concentrations, independent of nivolumab co-administration.
The Sweet Spot: 1.34 mg
Digging into the data, our exposure-response model highlighted a key finding: a 1.34 mg dose of Tivozanib delivers the greatest anti-tumor activity. Compare that to a 0.89 mg dose paired with another drug, and the higher dose stands out—especially when the second drug adds no benefit. Patients on 1.34 mg showed numerically improved progression-free survival (PFS), a trend we confirmed in the analysis.
This underscores a broader point: optimizing TKI dosing isn’t just a technical detail—it’s a game-changer for patient outcomes. Tivozanib shines here, with less than 20% of patients requiring dose reductions at 1.34 mg (taken 21 out of 28 days). Its tolerability makes it an appealing option.
Tackling Hypertension Head-On
Hypertension is a common hurdle with TKIs, and Tivozanib is no exception. But here’s the good news: early intervention works. By monitoring patients regularly and optimizing blood pressure before it spirals, we can maintain that optimal dose. Dose matters—starting high and adjusting for toxicities is the strategy that keeps Tivozanib effective.
From Trials to Tomorrow: The Strike Trial
This analysis isn’t just a snapshot—it’s a stepping stone. Take the Alliance A032001 (Strike) trial, which explores Tivozanib with or without embolism in the adjuvant treatment of high-risk RCC. After seeing these results, we opted for the higher dose in the trial, confident it pairs well with immunotherapy without amplifying hypertension risks.
This builds on insights from Contact-3, where cabozantinib plus atezolizumab didn’t outperform cabozantinib alone in immunotherapy-progressed patients. Despite differences—like using a PD-1 inhibitor in our study—the takeaway was consistent: adding immunotherapy to a TKI post-progression doesn’t boost outcomes. Monotherapy, optimized, remains king.
Why Tivozanib Stands Out
What makes Tivozanib compelling? It’s well-tolerated, with a favorable safety profile that supports its use at higher doses. This analysis reinforces that optimizing TKI doses as a monotherapy is our best bet with current drugs. It’s data that doesn’t just augment clinical results—it drives them forward.
Looking Ahead
As we advance RCC care, especially in the adjuvant setting, trials like Strike are critical. It’s asking: Does a short course of full-dose Tivozanib with a year of embolism improve outcomes over embolism alone in high-risk resected RCC? The answer could reshape standards of care—and this data suggests we’re on the right track.
I encourage the oncology community to support Strike, open through Alliance. Together, we can refine how we treat RCC and deliver the best for our patients.
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