Advances in Frontline Treatment for Advanced Renal Cell Carcinoma - Episode 4

Selecting a Treatment Regimen for Favorable Risk Advanced Clear Cell RCC

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Moshe Ornstein, MD, MA, explains the factors he considers when deciding on a combination treatment regimen for a patient with favorable-risk advanced clear cell RCC.

Nizar Tannir, MD: Moshe, do you think this was an appropriate regimen to choose for this patient? What’s your take on how we select patients? Do you use the IMDC [International Metastatic Renal Cell Carcinoma Database Consortium] criteria when you see your patients in the clinic for risk stratification? I’d like to ask you this tough question: Is there a role for a single-agent TKI [tyrosine kinase inhibitor] for these patients with favorable-risk disease? Would you like to comment on that?

Moshe Ornstein, MD, MA: All great questions. The first thing I think about, especially in a patient who has favorable-risk metastatic RCC [renal cell carcinoma], is whether the patient is appropriate for surveillance. We know that there’s a subset of patients, especially those with 0 to 1 IMDC risk factors and relatively low volumes of disease, who don’t need treatment right now and can be watched. That’s the first question I ask myself. Of course, in a case like this, it’s hard to see the previous scans and all of the patient’s symptoms, but it’s an important point to highlight. But assuming that this patient’s disease burden is growing, even if there are only some symptoms, treatment is appropriate.

In my clinic, although I ask my fellows to make sure they know the IMDC risk criteria, and although the IMDC risk criteria are critical when it comes to patient selection and payer selection—we’re going to try to get drugs approved through the insurance companies; ipilimumab and nivolumab isn’t approved for favorable-risk metastatic RCC—things that don’t necessarily fall within the IMDC criteria play a role in my decision-making. These include liver and bone metastases, even if it’s favorable risk, a weakening performance status, some weight loss, lack of appetite, and lack of energy.

But ultimately, we follow those IMDC risk criteria in helping to select treatment options. I agree with what Dr Tykodi said. Once I’m picking a regimen [for someone with] favorable risk, it would be one of the IO [immunotherapy]/TKI regimens. For patients who are young and healthy and don’t have other major comorbidities, I tend to favor lenvatinib and pembrolizumab up front, much as in this case, because of the efficacy end points demonstrated in the trial. However, for those patients whom I’m a little more concerned about their comorbidities or the ability to tolerate such a high dose of a TKI, I may favor one of the other options.

I made a note during the presentation about that question of using a single-agent TKI. There are those who would select the single-agent TKI, especially for a patient with favorable-risk metastatic RCC. It’s my general practice to not give a single-agent TKI. If we’re going to reach a decision where a patient needs treatment, then we should give a treatment that has an immunotherapy backbone to it. We don’t cure patients with single-agent TKI [therapy]. The benefits generally aren’t as long-lived as they are with an IO mixed in with that TKI. My general approach is to give the combination, picking 1 of the 3, but not to give a single-agent TKI.

Transcript edited for clarity.