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Research / Trials

KCCure interviews Dr. Mike Atkins about the TIVO-3 trial

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In the last decade, the number of approved therapies for kidney cancer has rapidly grown from just a few FDA approved treatments to over ten. Yet despite more options, the disease in some patients is still resistant to standard treatment. AVEO Oncology aims to change that.

In May of 2016, AVEO Oncology launched the TIVO-3 trial – a randomized, open label study that compares Aveo’s drug tivozanib to an already approved drug sorafenib (Nexavar). The trial will enroll over 300 patients at multiple centers around the country.

KCCure sat down with Dr. Michael Atkins, Deputy Director of the Georgetown-Lombardi Comprehensive Cancer Center in Washington, DC to talk about the TIVO-3 trial and what it means for kidney cancer patients.

Since joining the Georgetown-Lombardi Comprehensive Cancer Center in 2012, you’ve vastly expanded the number of clinical trials available for patients with kidney cancer being treated at your center, including the TIVO-3 trial. Why do you think it’s so important for patients to have access to clinical trials?

Atkins: Clinical trials in many cases provide patients access to tomorrow’s treatments, today. All of the 10 agents that have been approved for the treatment of patients with renal cell carcinoma (RCC) over the past 11 years were initially studied in clinical trials.  Patients who participated in those trials received better therapy than could be provided through FDA approved standard of care methods available at the time.

Although we have made great progress in the treatment of patients with advanced RCC over the past decade, the majority of patients still ultimately die of their disease and therefore better treatment approaches are needed if we are to “cure” the majority of patients with this disease. Clinical trials give patients access to the most promising of new approaches.

Tivozanib is a tyrosine kinase inhibitor or TKI. We already have five other TKIs that are approved for kidney cancer. What’s the advantage of approving another drug that falls into that category?

Atkins: Tivozanib is the most selective and arguably the most potent of the second generation VEGFR tyrosine kinase inhibitors (TKIs). For patients who experienced significant toxicity from TKIs leading to a dose reduction and/or whose disease progresses on first and second line agents, tivozanib might be an alternative approach for providing effective and tolerable VEGF pathway blockade.

The TIVO-3 trial randomly assigns patients to tivozanib or sorafenib (a first generation TKI). The hypothesis that the trial is testing is that a more selective VEGFR TKI such as tivozanib will provide more efficacy and less toxicity than less selective VEGFR TKIs such as sorafenib.

Selective and Potent – those are two words that we often hear doctors mention when describing targeted therapies. Can you define those terms and explain how they impact patients who are being treated with these therapies?

Selectivity is the degree to which a dose of a drug produces the desired effect in relation to adverse effects. In other words, a more selective drug, relatively speaking, will result in more anti-tumor activity with fewer side effects.

A highly potent drug means that we see a stronger anti-tumor response at a lower concentration. A potent drug like tivozanib can be prescribed in lower doses – as compared to older, first-generation drugs that need to be prescribed in higher concentrations.

While TKIs can be very successful in stopping cancer from growing, the side effects from these drugs can be harsh. How does tivozanib differ in terms of side effects and overall toxicity?

Atkins: Getting back to the selectivity of the drug, tivozanib more cleanly blocks VEGFR signaling and therefore it appears to have fewer “off target” side effects, (i.e. hand-food syndrome, diarrhea), than other multi-kinase inhibitors such as sunitinib (Sutent) or pazopanib (Votrient) in use today. Typical side effects for tivozanib include hypertension and dysphonia (hoarseness in voice) which are directly related to its anti-tumor mechanism of action (e.g. blocking the VEGF receptor).

The TIVO-3 study is being offered at the Georgetown-Lombardi Cancer Center as well as 80 additional centers around the globe. Interested in learning about eligibility and locations? Click here to find a center near you.

Michael B. Atkins, MD, is the Deputy Director of the Georgetown-Lombardi Comprehensive Cancer Center in Washington, DC and William M. Scholl Professor and Vice Chair of the Department of Oncology and Professor of Medicine (Hematology/Oncology) at Georgetown University School of Medicine. Previously, Dr. Atkins was the leader of the Kidney Cancer Program at the Dana-Farber/Harvard Cancer Center and Professor of Medicine at the Harvard Medical School. He served as Director of the DF/HCC Kidney Cancer Specialized Program of Research Excellence (SPORE) grant and co–principal investigator of the DF/HCC Skin Cancer SPORE. 

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