Risk Stratification Influences Choice of Frontline IO/TKI Regimen in mRCC

Rana McKay, MD

Associate Professor of Medicine

University of California San Diego​

San Diego, CA​

DISCUSSION QUESTIONS

• How do you assess risk status in clear cell metastatic renal cell carcinoma (mRCC)? ​
• Is risk status alone the deciding factor in your first-line treatment decision making?​​

RANA MCKAY, MD: How do you think about favorable vs borderline intermediate-risk patients? What if they had mild anemia [but otherwise favorable risk], so they’re intermediate risk? How do you categorize them? How do you think about the intermediate- and high-risk cohort?

DARSHIL SHAH, MD: The main [factor] is deciding on performance status and other risk factors like anemia, hypercalcemia, etc. Then over time, you have a [regimen] that you’re comfortable with, whether it’s cabozantinib [Cabometyx] plus nivolumab [Opdivo], or axitinib [Inlyta], which is fairly well tolerated so we’ve been using that for a while. It’s a mix of the patient in front of you and what you’re comfortable with that would be the deciding factor.

MCKAY: I like that, thinking about burden of disease, performance status, and having 1 go-to regimen that you feel comfortable in using when you’re going for treatment.

PAMELA MIEL, MD: For risk status, you [should] also include how soon after the initial diagnosis the patient developed metastatic disease, whether it’s de novo or it was over a year. Then [consider] the anemia, hypercalcemia, etc. Risk status is important in deciding which first-line treatment to pick; cabozantinib/nivolumab and the dual immunotherapy seem to be acceptable for both good risk vs intermediate and high-risk disease.

Sometimes, what determines which one you choose is insurance status.Sometimes they give a hard time with dual immunotherapy, so you end up doing a tyrosine kinase inhibitor [TKI] with immunotherapy [IO]. Also, [I consider] what the patient wants. If the patient wants to do an oral medication, you can give [the TKI] and then add IO. Sometimes they just prefer to do intravenous IO and not worry about having to take medications at home.

MUHAMMAD ANAS TARAKJI, MD: One thing I worry about when I choose my first line is what I’m going to give in the second line. I know there are a lot of data for cabozantinib/nivolumab for patients with [favorable] risk, and there’s no recommendation from the National Comprehensive Cancer Network for nivolumab plus ipilimumab [Yervoy], which I usually use, but then if the patient’s [disease] progresses, what are you going to use, if you used the doublet [IO] in the first line?¹ At least I would have the TKI, for example single-agent cabozantinib, to use in the second line.

DISCUSSION QUESTION

• What drives your selection of first-line therapy in favorable-risk disease? ​

MCKAY: Do you give nivolumab/ipilimumab for patients with favorable risk, or do you tend to stick with IO/VEGF-TKI?

ROBERT YOO, DO: Based on the [prior data from] the CheckMate 214 trial [NCT02231749], I don’t use ipilimumab/nivolumab for the favorable risk group.² I stick with the data. I always use cabozantinib/nivolumab or lenvatinib [Lenvima] plus pembrolizumab [Keytruda].

MIEL: For some of my [older] patients who live out of town, I’m using pazopanib [Votrient] and it’s worked very well for 3 years. I know it’s not standard of care anymore, but it’s still works very well. The patient can follow up with laboratory tests and [telemedicine] without even coming to the office. I have a patient who has been on pazopanib for 3 and a half years.

MING ZHOU, MD: In those with favorable-risk clear cell RCC, I don’t use IO. I try to save it for the possible later lines of treatments. Based on the preference, sometimes anti-angiogenic TKIs with better adverse event profiles for some of the older population would be favorable.

MCKAY: Excellent. Are others in the category of using more VEGF-TKI monotherapy? Or [are you] leaning towards more IO combination?

MIEL: I tend to give cabozantinib/nivolumab for first-line treatment in favorable risk mRCC.

MCKAY: The favorable-risk patients are usually asymptomatic, doing quite well, and have multiple options at attempting to see second- or third-line [therapy]. I think the number of patients that you lose upfront, who never see second line, is lower in this population. That colors decisions around what kind of therapy you give.

_References:

_{1. NCCN. Clinical Practice Guidelines in Oncology. Kidney cancer, version 2.2024. Accessed February 7, 2024. http://tinyurl.com/3f4zyez9}

_{2. Escudier B, Motzer RJ, Tannir NM, et al. Efficacy of nivolumab plus ipilimumab according to number of imdc risk factors in CheckMate 214. Eur Urol. 2020;77(4):449-453. doi:10.1016/j.eururo.2019.10.025}