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


During a Targeted Oncology™ Case-Based Roundtable™ event, Rana McKay, MD, moderated a discussion on what role risk stratification plays in selecting frontline therapy for a patient with metastatic renal cell carcinoma. This is the first of 2 articles based on this event.

Rana McKay

Rana McKay, MD

Associate Professor of Medicine

University of California San Diego​

San Diego, CA​


  • 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.


  • 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.


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

Related Videos
Related Content