Next-Generation Therapies in RCC: Examining Tivozanib and Belzutifan

Katy Beckermann, MD, PhD, of Vanderbilt-Ingram Cancer Center, and Thomas Hutson, DO, PharmD, FACP, of Baylor University Medical Center, compare the relative toxicity and quality-of-life data for tivozanib versus belzutifan in patients with relapsed or refractory advanced RCC. They also consider how certain combinations may “move up” in the treatment paradigm and resulting sequencing implications.

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Katy Beckermann: Dr. Laurence Albiges presented the LITESPARK-005 data at ESMO, which recently led to the approval of belzutifan here in the United States. Dr. Thomas Powles also presented quality-of-life data, showing a similar situation where we see a certain patient population experiencing a durable effect, potentially enhancing the quality of life for RCC patients who have undergone prior treatments. Now, I will turn to you and ask, considering that data and then seeing this tivozanib data, how do you relate those or how do you think about that in your clinical practice?

Dr. Hutson: I think we are in a fortunate position with an abundance of choices. However, anyone treating kidney cancer today exposes their patients to powerful therapies, often accompanied by significant side effects. This is evident in trial reports where two-thirds or more of patients require dose reductions to continue therapy, despite the efficacy of these treatments. Emerging therapies like tivozanib and belzutifan may not necessarily have the tumor shrinkage ability of drugs like len/eve and cabozantinib. It would be interesting to conduct head-to-head trials to compare their efficacy.

However, the goal for patients receiving these drugs in second and third-line settings may differ, especially as we move into later lines of therapy. Combination approaches, such as TiNivo-2, are also being explored. Tivozanib offers a different PK profile compared to drugs like axitinib, with potential benefits in terms of side effect management. Belzutifan, on the other hand, might shine as part of combination therapy, such as len/pembro.

As we await results from ongoing studies, it is clear that tivozanib remains a valuable option in the refractory setting. Patients are often ready for it, seeking relief from side effects while maintaining benefits like stable disease and improved quality of life. Educating colleagues about its potential as a first-line therapy is crucial, considering the abundance of treatment options available.

Katy Beckermann: Indeed, it is a promising time for kidney cancer patients, with numerous therapy options available. I wonder if there are specific clinical features or trial data that guide your decision-making process, especially for patients in later lines of therapy where biomarkers are lacking?

Dr. Hutson: For me, the sequencing off a trial dictates the initial choice, typically involving len/pembro as a first-line option. Tivozanib fits well as a third-line option, complementing other drugs like cabozantinib or lenvatinib. Choosing between tivozanib and belzutifan in later lines can be challenging, but my goal is to expose patients to both agents whenever possible. Factors like time to response may influence my decision, but ultimately, I aim for patients to benefit from a range of effective therapies.

Katy Beckermann: Agreed. I hope all my patients can access these effective treatments. The future seems promising, especially with the exploration of novel combination therapies. Is there anything else you would like to highlight about this?

Dr. Hutson: Both tivozanib and belzutifan show promise as treatment options. I am particularly interested in ongoing studies exploring combination therapies and the potential of third-generation therapies to overcome resistance and enhance treatment outcomes. My focus is on pushing the field forward, offering patients the best possible care through innovative treatment strategies.

View their previous comments on Insights From the TIVO-3 Study.