Dr Alan Tan on the Options for Patients With Advanced RCC

In the second part of this discussion with The American Journal of Managed Care® (AJMC®) on renal cell carcinoma, Alan Tan, MD, discusses the challenges of treating advanced renal cell carcinoma, taking into account patient quality of life and minimizing toxicities. Tan is an assistant professor in the Division of Hematology, Oncology and Cell Therapy at Rush Medical College and is also the director of GU Medical Oncology. He specializes in kidney cancer, bladder cancer, prostate cancer, and melanoma.

AJMC®: Let's discuss some of the patient outcomes with advanced renal cell carcinoma. What is the 5-year survival rate of RCC? And how does that compare to patients who have the advanced disease?

Tan: If caught early, the prognosis can still be quite good. The 5-year survival could be 80% to 90% if caught early. But if caught in late stages, metastatic disease, 5-year survival is probably going to be 5% to 10% without good therapies. But of course, we have good treatments now that is raising that. We don't have that long a follow up, but the longest part we have is with immunotherapy combination with ipilimumab and nivolumab. And I think we would probably be able to predict that 30% of people now are alive at 5 years and possibly cured with immunotherapy combinations.

AJMC®: In your opinion, what are some of the greatest challenges associated with treating advanced renal cell carcinoma?

Tan: Even though we're having a lot of success with these immunotherapy combinations, where we can possibly cure some of these patients too, for the majority of patients, they're not being cured. Seventy percent of the patients are still going to die of their cancer, even if they're getting some of these novel treatments. So that's the major challenge. We need to raise that bar even higher. And so if they're not cured, they're going to require second-line, third-line therapy, and we're studying that currently. But the second, third-line, fourth-line setting is kind of mixed. It really depends on what you started with, what treatment you started with, and asking, do you throw the whole kitchen sink at them all at once, give them all your strongest drugs at once? Or do you sequence them and try to think of it like a marathon instead of a sprint? I don't think we know. I think in general in oncology, we like to give all our best drugs, use up all of our best drugs in the frontline. And then, if they're not cured, then use something later lines for palliation. Drug resistance, of course, is a problem and we don't have biomarkers for kidney cancer. For all the other cancers, we are doing pretty well as far as predicting biomarkers. But if we do genomic testing, PD-L1 testing, all of those things for kidney cancer, it really is not helping us. It's not really helping us make decisions on who to select.

AJMC®: How do you approach managing toxicities, and perhaps the flip side of that, optimizing patient quality of life as you're selecting therapies and working with patients on their advanced renal cell carcinoma?

Tan: Great question. Going back to how common kidney cancer, when I first started practicing general oncology, I wasn't seeing much kidney cancer. I had strong interest in it, but you might see a couple of cases a year or so. And I interviewed people from the community and they don't really have that much experience with kidney cancer to know how to be an expert at it. But now being an expert in kidney cancer, you really have a lot of experiences with the trials and tribulations of management. And I think over time you develop a skill set. And knowing what to use in the frontline setting, when you have all these options, is an art and based on previous experiences. But treatment-related toxicities, you're asking, can be all immunotherapy based if you use something like ipilimumab-nivolumab. And I also specialize in melanoma. These are kind of close cousins using the same kind of treatments that have high risk of immune-related toxicities.

First thing I would say is educating the patients, because if the patient knows what to expect, and why things happen, then they're more likely to call you or approach your clinic with these concerns before it becomes too late. Sometimes patients may let it escalate too much and then you have the grade 3/4 toxicities that become very severe and the patient might be off treatment for a long period of time. So in general, that’s the first step. But as you know, there's a long list of immune-related adverse events that can happen. And the most common are like skin toxicities, thyroid, you know, hyper- or hypothyroidism, the quality-of-life ones like the arthralgias, rheumatoid arthritis type symptoms, but then you have the unlucky patients that get the super rare ones that, you know, you often don't see that much. But if you treat hundreds of these patients, you're going to see them eventually like hypophysitis, etc. Immune related hepatitis is, you know, not that common, but it can happen. And some of the ones that are challenging like pneumonitis, this can often present to the emergency room similar to pneumonia, or COVID symptoms, etc. So really educating the patient so that the patient can educate the emergency room attending, that "This is what I'm on and you should probably call my oncologist and he or she can explain those toxicities and, you know, see if that might be contributory." And then the TKIs have their own toxicities, right? We have longer experience with tyrosine kinase inhibitors and those can include hypertension, really high refractory hypertension, or hand-foot syndrome. These things also affect wound healing and increase the risk of thrombosis like I mentioned earlier. But just you know, a long list of different kinds of toxicities, including gastrointestinal, nausea or constipation, et ctc.

AJMC®: In closing, what are you working on in renal cell carcinoma that you're excited to share?

Tan: I'm very interested in biomarker development. And I think there's a highly unmet need in kidney cancer, where we're trying to look outside of the box, looking at circulating biomarkers like ctDNA. So in a high-risk patient as a patient that had surgery, could they potentially be spared of 1 year of adjuvant immunotherapy treatment that could be potentially very life altering if they get a grade 3/4 event? We only treat the patients that really need it, and spare the patients that are likely at low risk for a recurrence. I think that's one focus that I'd like to mention. But also in the metastatic setting, finding the biomarkers that really help us decide, should we get immunotherapy combination with an immunotherapy only, what we call I/O-I/O, or is the patient better off doing I/O plus TKI? And, you know, where is the role of triplet therapy? We have a study that has 3 drugs, and I don't think right now that should be the standard of care, but maybe there's a biomarker that tells us that a certain triplet therapy may be better. And there's other novel therapies that we're excited to combine with. We're trying to move in the ones that are exciting in the third line setting up to the frontline setting or adjuvant setting. And I think that's where we're, you know, going to see the future at. And, you know, there's other exciting technologies like bispecific antibodies, CAR-T cell cellular therapy, that may be exciting to use in the frontline setting in the future, including radioligand therapy.