Risk Stratification Influences Approach in Frontline Advanced RCC Care

Benjamin Garmezy, MD (Moderator)

Assistant Director of Genitourinary Research

Sarah Cannon Research Institute at Tennessee Oncology

Nashville, TN

DISCUSSION QUESTIONS:

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

BENJAMIN GARMEZY, MD: There are 2 main risk calculators that are used. There are the IMDC [International Metastatic RCC Database Consortium] and the the MSKCC [Memorial Sloan Kettering Cancer Center] tools. Some oncologists use more of a clinical gestalt, [looking at] what the patient looks like in front of them, instead of going through and clicking the buttons and putting that in their notes. Are you using risk stratification in your clinic, or are you looking at the patient in front of you?

KETAN DOSHI, MD: I use it [because] our electronic medical record asks for it.

UDAY DANDAMUDI, MD: I usually do the IMDC calculation by myself to determine what kind of treatment, whether it is for favorable or unfavorable risk. If they have favorable risk, I use either a single-agent tyrosine kinase inhibitor [TKI], the combination of nivolumab [Opdivo] and cabozantinib [Cabometyx], or lenvatinib [Lenvima] plus pembrolizumab [Keytruda]. If they have high risk or intermediate risk, then I use a dual IO [immunotherapy] combination.

GARMEZY: Sometimes people say that [they are not using risk stratification], and I think it's often reasonable because if you're going to use an IO/TKI combination, it might provide some prognosis, but doesn't always inform the therapeutic decision-making for all the oncologists out there.

DISCUSSION QUESTIONS:

• What drives your selection of first-line therapy for favorable-risk clear cell mRCC? ​
• Do you consider the balance of efficacy/quality of life/safety?

GARMEZY: When we go into the calculator, those risk scores are based on white blood cell [counts] and things like that. But what are the most concerning [factors]? Is it the distribution of the geography the metastatic disease? Is it the pace of the metastatic disease? Is it the bulk? Is it performance status? Is it laboratory results? What is it that most scares you that a patient's not going to do well?

SIMON BLANC, MD: I look at bulk [and pace of] progression. In a lot of cases, patients come to me at diagnosis; they [may have] had it in the past…[and] started treatment somewhere else. I also use MSKCC. It's a combination of everything: performance status, age, [etc]…. I get more wary of visceral metastases as opposed to bone metastases.

GARMEZY: [For those, who would use] IO doublet in patients with favorable risk? There are a lot of physicians using it. It's very reasonable and it's not category 1 for the National Comprehensive Cancer Network, but it is listed there.¹

JORGE HURTADO, MD: I [would consider using] lenvatinib/pembrolizumab [in patients with favorable risk]. In the [CLEAR trial (NCT02811861)], it had [one of the] highest proportions of patients with favorable risk, and also had a higher complete response rate and the highest overall response rate.² I always think about it, whether I am doing the right thing or not, because when you look at all the 3 trials with TKI and IO, the patients with favorable risk do as well with either [treatment]. But…that chance of a complete remission or that profound response may be long run because, [for] these patients who have good risk, maybe they do well anyway, [but it] might make a difference. I have a low threshold to discontinue if I see the patient is having a tough time.

GARMEZY: Does anyone ever not start therapy on a metastatic favorable-risk patient?

BLANC: Yes, [if they are] much older and have poor performance status with very slow disease. I have a patient who would develop a metastasis every 2 or 3 years; it would be an oligometastasis and I would [use stereotactic body radiation therapy], and the patient was doing fantastic. I have another patient who has a lot of metastases but hasn't progressed in 3 years. The short answer is ‘watch and wait’ is an option in a lot of patients with only favorable [risk]; I always treat those with intermediate and poor risk.

GARMEZY: Radiation in oligometastatic disease to delay systemic therapy is an option as well, [though] probably less commonly used. There's a phase 2 data set out of The University of Texas MD Anderson Cancer Center that suggests it's reasonable.³ I've done it a few times, and I've done it successfully, but patient selection is key. It’s probably underutilized. Historically, clear cell RCC was thought to be radio-resistant, but it's not. You just have to dose it right and work with a radiation oncologist who has treated patients with RCC. That doesn't mean that the radiation oncologist has to be a kidney specialist. You don't [have to] send your patient to Houston or New York City, it just means they have to be familiar.

_References:

_{1. NCCN. Clinical Practice Guidelines in Oncology. Kidney cancer, version 1.2024. Accessed October 10, 2023. https://tinyurl.com/3f4zyez9}

_{2. Motzer R, Alekseev B, Rha SY, et al. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 2021;384(14):1289-1300. doi:10.1056/NEJMoa2035716}

_{3. Tang C, Msaouel P, Hara K, et al. Definitive radiotherapy in lieu of systemic therapy for oligometastatic renal cell carcinoma: a single-arm, single-centre, feasibility, phase 2 trial. Lancet Oncol. 2021;22(12):1732-1739. doi:10.1016/S1470-2045(21)00528-3}