Initial Therapy for Advanced Renal Cell Carcinoma - Episode 9

Treatment Options for Intermediate/Poor-Risk RCC


Eric A. Jonasch, MD: The biggest thing that I look at in an individual who I’m considering for frontline systemic therapy for clear-cell renal cell carcinoma with intermediate- and poor-risk features is, can they tolerate ipilimumab and nivolumab? I would choose that combination first because of the fact that it has the highest complete response rate and cure fraction.

The challenge really is that there is a subset of individuals who, if they were to develop some of the adverse effects like colitis, nephritis, or hepatitis, may not have a physiological reserve to really be able to sustain those toxicities and be able to get through them. So that’s the first question that I ask. For those individuals for whom the answer is yes, they could, I will give ipilimumab and nivolumab. For individuals who wouldn’t tolerate it, I would give axitinib and pembrolizumab. For those individuals for whom there are some absolute contraindications to giving I/O [immuno-oncology] therapy, I would give cabozantinib.

Elizabeth R. Plimack, MD: The conversation we have when we first meet a patient with intermediate- or poor-risk kidney cancer has become relatively straightforward in our practice. The data for axitinib and pembrolizumab are so robust that outside a clinical trial—and we do have trials in this space that we offer—it’s really what we recommend. And that’s for response rate and overall survival to be maximized. Generally, with intermediate- and poor-risk disease, we know if we don’t initiate treatment, the cancer will grow relatively rapidly. We know that from the prognostic curves. So it’s a pretty straightforward conversation where that’s typically what we recommend.

There may be some patients who don’t want treatment or some patients with autoimmune conditions that put them at a very high risk for adverse events with immunotherapy. Obviously, every situation has its nuances and has to be carefully considered. But in general, for intermediate- and poor-risk disease, I think until there are better data than axitinib-pembrolizumab. That will be our recommendation.

Eric A. Jonasch, MD: When we look at the 3 trials that underpin intermediate- and poor-risk patients in the frontline setting, it’s really going to be the CABOSUN trial, KEYNOTE-426, and CheckMate 214.

In CheckMate 214, up to 60% of individuals needed to take steroids at some point, and over 30% of these individuals. had to take greater than 40 mg of prednisone equivalent per day. There’s clearly a lot of I/O toxicity there. In the KEYNOTE-426 study, these numbers were considerably lower; they were in the low teens. Overall that regimen was quite well tolerated.

In the CABOSUN trial, cabozantinib didn’t look like it was very different from sunitinib from a tolerability perspective, and it was really what we expect with these types of TKIs [tyrosine kinase inhibitors]. The distinguishing feature really here is the rate of I/O toxicity in the ipilimumab-and-nivolumab regimen versus the axitinib-and-pembrolizumab combination.

Transcript Edited for Clarity