Initial Therapy for Advanced Renal Cell Carcinoma - Episode 7

Favorable-Risk RCC: Options for VEGF TKI Monotherapy


Elizabeth R. Plimack, MD: Selecting VEGF inhibitors is a little tricky. They are similar in theory. The list of adverse effects the patient reads is almost identical drug to drug. But the adverse effects they get from a given drug vary, and how well the drug works can vary. I’ve had patients who have had their cancer grow right through, for instance, pazopanib, and then we add in cabozantinib and the tumor shrinks, and they have much more time on that.

I’ve had the reverse occur where after a long run of pazopanib, we try cabozantinib and it really doesn’t buy them anything additional. I wish we knew biologically what was going on and how to explain that, but I think it’s much more picking your first drug, then trying a second, then trying another. They all are a little different. The 1 that’s the easiest for me to get to a tolerable dose for patients is axitinib, mostly because it comes in 1-mg tablets, so we can really fine-tune the dose patient to patient.

Eric A. Jonasch, MD: In the frontline favorable-risk setting, sunitinib and pazopanib are pretty interchangeable. Now there’s been an evolution in how we use these agents. Sunitinib officially is given 4 weeks on and 2 weeks off. But very few people are doing that now.

We and others have published that if you give sunitinib 2 weeks on and 1 week off, it’s better tolerated and there’s some evidence that people might actually be doing better, although we don’t have randomized data to prove that. But the same is true also for pazopanib. Although this drug is supposed to be given daily continuously, people are now taking breaks when they’re taking this agent, and overall the tolerability of these antiangiogenic agents has improved compared with historic controls. This is really because both patients and physicians know how to use them better.

Elizabeth R. Plimack, MD: When we choose to start single-agent VEGF inhibitors in renal cell carcinoma, my first choice is pazopanib based on the COMPARZ data, which compared pazopanib with sunitinib, both approved frontline agents. They have similar overall survival. Pazopanib was much better tolerated, and so we really have leaned on those data, because those data came out, and use that as our single-agent VEGF inhibitor of choice. There are some data with axitinib in the frontline setting, but it’s surprisingly not as robust in cross comparison. The other advantage to pazopanib over sunitinib is that the consistency of dosing allows for consistency of dosing of a patient’s other medications, like their blood pressure medications, which would need to go up and down based on whether someone was on drug. Sunitinib in contrast is dosed in an on-off fashion. There are different ways to do that, but as part of the drug, we know it’s best used on and then off. That just becomes more cumbersome to manage other medications.

Eric A. Jonasch, MD: In thinking about some practical advice to give about how to use VEGF TKIs [tyrosine kinase inhibitors], I have to say that they’re pretty similar in terms of their overall toxicities, although there are some unique features. For example, pazopanib has hepatitis to a higher degree compared with sunitinib or cabozantinib. In my experience cabozantinib has potential for more devastating fatigue than the other 2. This is also true for axitinib, the companion for pembrolizumab, and nivolumab.

The guiding principles here really are that we need to make sure that when individuals develop adverse effects, they should take breaks. It’s important that they let the normal tissue biologies recover, and that’s probably going to recover faster than the tumor is going to be able to start growing. By doing this, we’re going to end up allowing individuals to have higher area under the curve long term in terms of dosing, and we are to likely benefit from these agents more.

Transcript Edited for Clarity