Frontline TKI in Intermediate-Risk Renal Cell Carcinoma - Episode 3
As we talked about in this case, this patient has a history of ulcerative colitis. And so the concern is with a history of autoimmune disease, is an immunotherapy option really the preferred approach? We know immunotherapy works by trying to rev up the immune system, and a common toxicity is immune-related adverse events where you get autoimmune toxicities. And if you have an underlying autoimmune disease, there’s certainly a concern. These patients were excluded from the clinical trials that led to their approval.
There have been retrospective data led by Lauren Harshman, MD, at Dana-Farber Cancer Institute, showing that in patients with history of autoimmune diseases, looking at those with urothelial carcinoma or renal cell carcinoma, immunotherapy can be given to these patients safely with expected immune-related adverse events. But obviously, that’s always a concern when looking at these patients.
So in someone who has a history of active ulcerative colitis, who is on ongoing therapy, if they’re needing steroids, or they’re needing disease-modifying agents, I think you have to be worried about the toxicity of immunotherapy, especially when we have other options in the frontline. In someone like this, I think if you are going to elect treatment, a drug like cabozantinib would certainly be very appropriate when there’s that concern for immunotherapy, with the thought being you start with cabozantinib, if you don’t get the response, then you could certainly entertain immunotherapy in the second-line, potentially a monotherapy, given that’s where nivolumab is approved.
I think one of the questions before you start treatment is can you offer surveillance? Does this patient actually need therapy? This is something, especially with good-risk disease, where surveillance is certainly an option. And it’s actually been studied in a prospective study by Brian Rini, MD, and colleagues that’s published that showed that for patients with renal cell carcinoma, surveillance is a reasonable option.
In their study, the median time off therapy was just around 15 months. Looking at that specifically, the number of metastases, IMDC [International Metastatic Renal Cell Carcinoma Database Consortium] risk stratification were helpful in determining who would be the best for surveillance. So I think surveillance is certainly a reasonable option in someone who has good-risk disease. It’s something to always entertain. In this patient, you could argue that potentially his mild anemia could be from this ulcerative colitis. And with relatively asymptomatic patients, you could certainly offer surveillance in that situation. But I think with the number of metastases he has, bone metastases, I think therapy is very reasonable.
In this situation I think I would think about systemic therapy. To further support the role of cabozantinib, I think one of the things we know in renal cell carcinoma that is challenging is the presence of bone metastases. Those patients with bone metastases tend to have a poorer response to systemic therapy. And what’s been seen in cabozantinib, both in the CABOSUN as well as the METEOR trials, is it does have activity in bone metastases. So in those patients who have bone metastases, which may be historically resistant to some other targeted therapies, cabozantinib certainly plays a role in those patients.
Transcript edited for clarity.
Case: A 70-Year-Old Man with Intermediate-Risk RCC
A 70-year-old Caucasian man presented to ER complaining of blood in his urine and abdominal pain.
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