Advanced Renal Cell Carcinoma and Brain Metastases

Sumeet Bhatia, MD: In your practice, what do you do with patients with brain metastasis? Do you handle them any differently or how does that guide your decision-making?

Eric Jonasch, MD: It’s an evolving field with regard to understanding what we should be doing for these individuals. I’ve been using cabozantinib-nivolumab for these individuals, and we’re learning more and more about lenvatinib and pembrolizumab. The things we’ve learned over the years with the use of TKIs [tyrosine kinase inhibitors] and individuals where you’re worried about bleeding is that they do the opposite. That’s absolutely not true for bevacizumab. Bevacizumab is a drug that will increase the bleeding risk substantially. But we found that in individuals who would have had brain metastases that we put on TKIs like cabozantinib or, more recently, lenvatinib, these agents seem to affect the central nervous system. The older regimens didn’t seem to have that [effect on the central nervous system], especially in combination with immunotherapy.

We have a fellow who’s working with me, Elshad Hasanov, who has accumulated the world’s largest collection of brain metastases specimens. We’re trying to understand more about what actually drives brain metastases and what the best treatments are. That’s how we’ve been doing it at this point in time. In the early days, we needed more data. There’s certainly nothing wrong with treating an individual, with ipilimumab-nivolumab. Some data that have come out of France showing that there’s a reasonable response rate with ipilimumab-nivolumab in the brain, in patients with renal cell carcinoma. But we could also consider an I/O [immuno-oncology]–TKI regimen.

Sumeet Bhatia, MD: These patients whom you treated with the TKI in that situation, were their brain metastasis controlled with radiation? Or were they untreated with the hope that immunotherapy was going to help in the brain? What was the thought process?

Eric Jonasch, MD: Because we can’t guarantee that these therapies are effective, we’ve used radiation therapy, stereotactic radiosurgery, to the lesions we should treat. And then we’ve added and made sure that these people get in an I/O–TKI care regimen. We’ve seen that they do not develop, and the rate of new lesion development seems to reduce dramatically. We’re doing a belt-and-suspenders approach using targeted radiation therapy as well as the combination therapies. One thing I try to avoid at all costs is whole-brain radiation therapy for individuals with renal cell carcinoma. It doesn’t seem to control the disease terribly well, and the neurocognitive effects long term can be quite devastating. That’s 1 thing I’m really trying to avoid.

Transcript edited for clarity.