Expert perspectives on the decision-making process for selecting frontline systemic therapy for patients with advanced renal cell carcinoma.
Chandler H. Park, M.D.: One of the toughest parts of being a kidney cancer doctor is we have four FDA-approved medication combinations to treat our patients who are diagnosed with Stage 4 kidney cancer. As I mentioned, the cancers spread to the lungs or the liver. Now, all four [treatments] have been through rigorous clinical trials, phase 3 trials with hundreds of patients, so they’re all effective. How do I determine which of those four treatments to give to the patients in front of me? As an oncologist and a cancer doctor, we’re all board certified in internal medicine, so we’re internists at the end of the day. So this is where we have to use our internal medicine background, i.e., primary care certification background.
The first decision I have to make is whether one of the four is a dual checkpoint inhibitor, i.e., immunotherapy alone. That’s called the nivolumab and ipilimumab. On the other side of the road are tyrosine kinase inhibitors [TKIs] and immunotherapy. When I see a patient, the first decision I have to make is, do I want to give an all-immunotherapy treatment or do I want to give an immunotherapy and a TKI?
Now let’s talk about the two immunotherapy combination treatments. Let’s say that the patient is symptomatic. Symptomatic means, as a physician, I’m looking at them and asking, do they have bone pain? Do they have abdominal pain? Whatever area the cancer is in, is there pain? Is their blood count low, i.e., their hemoglobin? We have something called the IMDC [International Metastatic Renal Cell Carcinoma Database Consortium] criteria. Now what do the IMDC criteria say? The IMDC criteria say the first thing I look at as a physician is, does my patient lie on a couch most of the day because cancer is causing a lot of symptoms? We have something called performance status. If they’re moving around really well, they get a score of zero. You have to add up the points and each point tells you if it’s intermediate, poor risk versus favorable risk.
The other thing that I look at is the blood level, called the CBC [complete blood count]. The CBC includes all the cells in the blood test. If their hemoglobin is low, that is one point. Now if their white blood cell count is high or if the platelet count is high, they’re each worth one point. So I add up the points. If they have zero points, that’s called favorable risk. If they have one or two points, that’s called intermediate risk. The poor risk is they have three or more of those points. The other way I add points, I forgot to mention, is if somebody had their kidney cancer removed by surgery and they haven’t had treatment in over a year, that’s considered zero as well.
Now based on the IMDC criteria, and based on performance status, when the kidney was diagnosed, is it less than a year or more than a year, hemoglobin, and white blood cell count of platelets. I put them into three buckets: favorable risk where they have zero on all those points, intermediate where there’s one to two and then poor risk if they have three. Now the favorable risk, I don’t give anybody in the favorable risk immunotherapy. That study was negative, and the benefit doesn’t outweigh the risk there. For favorable risk, I do immunotherapy and a TKI. For the intermediate risk and the poor risk, I look at the patient’s symptoms, are they asymptomatic? Do they have a lot of pain because of the cancer in the bones? Is their liver abnormal? Are they having trouble breathing? These are the things I look for if they’re symptomatic of cancer. I use a TKI and an immunotherapy because the TKI is much faster at controlling the cancer. And for the patients who may not have any symptoms and may have a low burden of disease, are when I think about the dual checkpoint inhibitor.
Tian Zhang, M.D., M.H.S.: In first-line treatment of metastatic or advanced kidney cancer, we often think about a lot of patient characteristics. Do they fall under the risk prognostication category of favorable risk disease, where their tumor and their clinical symptoms are not what we call inflamed? [Or] are they more in the intermediate and poor risk factors, or [using] IMDC criteria in which patients tend to have more inflammatory markers like anemia or high neutrophils or high platelets, as well as high calcium levels, which is a surrogate for bone metastases.
Based on those categories is how we currently assign systemic treatments in the front-line setting, and several immunotherapies with VEGF [anti-vascular endothelial growth factor] combinations as well as pure immunotherapy combinations are available across these IMDC tumor risk factor types. There is a pure immunotherapy combination called ipilimumab and nivolumab, which is used more for intermediate and poor risk disease [with] more inflamed tumors, and then VEGF and immunotherapy combinations more for favorable-risk disease, but also approved across all IMDC disease types. Those types in particular are agents like axitinib with pembrolizumab, lenvatinib with pembrolizumab, axitinib with ipilimumab, and cabozantinib with nivolumab. All four of those combinations are approved in the front-line setting.
Some key factors when selecting patients for these front-line therapies include the tumor burden. How much disease do they have, what are they presenting with, and how symptomatic are they? Do we need to look for early disease control, or are we shooting for durable responses over time? And then finally, patient comorbidities and their ability to tolerate some of the side effects of our treatments. For example, some patients with baseline autoimmune disease may or may not wish to undergo the potential immunotherapies that might activate their underlying autoimmune disease. Those are the things that we really think about when we’re talking through the right treatment combination for each patient in our clinics.
Transcript is AI-generated and edited for clarity and readability.