TIVO-3: Tivozanib as Third- or Later-Line Therapy in Clear-Cell RCC

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Experts from the Dana-Farber Cancer Institute delve into the TIVO-3 trial, discussing the design, outcomes, and nuances of tivozanib as a treatment option for refractory kidney cancer.

Summary:

In the context of a patient who progressed on cabozantinib and then received tivozanib as a third-line treatment, the discussion delves into the TIVO-3 trial, which led to the approval of tivozanib for refractory kidney cancer. Tivozanib, a VEGF receptor tyrosine kinase inhibitor (TKI), exhibits potent VEGF inhibition with fewer off-target toxicities compared to other TKIs.

The TIVO-3 trial showcased tivozanib’s superiority over sorafenib in patients with highly refractory kidney cancer, having received at least 2 prior treatment regimens. Although no statistically significant overall survival benefit was observed, there was a notable trend favoring tivozanib. The trial’s unique aspect was its inclusion of patients with advanced disease, reaching third- to fifth-line therapy. The discussion emphasizes tivozanib’s distinct toxicity profile. The potent VEGF inhibition correlated with increased hypertension compared to sorafenib, but notably, tivozanib exhibited lower rates of diarrhea and hand-foot syndrome. This differentiating toxicity profile suggests tivozanib as a potential option for patients intolerant to other TKIs due to dose-limiting toxicities such as diarrhea or hand-foot syndrome.

The experts acknowledge the significance of considering the trial’s control group, Sorafenib, which is not commonly used. The patient population in the trial, predominantly with ECOG performance status scores of 0-1, reflects relatively healthier individuals, prompting a discussion on the importance of patient health when interpreting trial results. The dialogue stresses that, especially in later lines of treatment, supportive care becomes a crucial consideration. For patients experiencing significant adverse effects or reduced tolerability, intensive supportive care, including hydration and palliative care, can be a viable alternative, potentially extending life as effectively as systemic therapy. In summary, the TIVO-3 trial establishes tivozanib as a valuable tool in refractory kidney cancer, offering a distinct toxicity profile that may benefit patients intolerant to other TKIs. The discussion underscores the importance of considering patient health, supportive care, and the evolving landscape of treatment options in advanced renal cell carcinoma.

Summary is AI-generated and reviewed by Cancer Network editorial staff.

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