Managing TKI-Related Adverse Events in RCC
An overview of adverse event and toxicity considerations with TKI therapies in renal cell carcinoma.
Transcript:
Elizabeth Wulff-Burchfield, MD: Dr McGregor, [I’ll] throw it to you. And again, everyone has provided such meaningful advice. Advice is the wrong word, but rather, a window into your own practices and interpretations of the data. One question I hear sometimes from colleagues who don’t treat a great deal of renal cell carcinoma is concern about immune-related adverse events [AEs] when considering nivolumab and ipilimumab. When I let that percolate a bit, it does make me think are there concerns about specific adverse events, or is it more about burden of toxicity overall that might factor into decision-making? Is there any patient profile for whom you’re really trying to avoid certain outcomes, besides [patients] who maybe have autoimmune disease? [Are there] any ways that AEs or toxicity factors in, except for the duration of exposure with TKIs [tyrosine kinase inhibitors]?
Bradley McGregor, MD: Yes, it’s a great question. What I would highlight is that we look at this here, and if we go back to that initial slide, one of the options was single-agent cabozantinib. We haven’t talked about that. I think that’s because, at the end of the day, the combination therapies are important in intermediate- and poor-risk disease. Cabozantinib showed improvement in PFS [progression-free survival] vs sunitinib. That was done in the era before combination therapies, so ultimately a combination therapy is my go-to. We can argue all day about ipilimumab vs IO [immunotherapy]-TKI, and which IO-TKI [should we use], but I don’t think anyone would disagree that in a patient who’s eligible for IO therapy, we should use something IO-based for these patients.
Then to the toxicity point, I think it is a real concern. The one factor that doesn’t get highlighted in the nivolumab-ipilimumab data is those rare but catastrophic issues. So those things that don’t show up, [such as] myocarditis, hypophysitis, adrenal sufficiency, or pancreatitis. Yes, these are rare, less than 1% or 2%, but they can happen with nivolumab-ipilimumab. And some of these endocrine toxicities can be lifelong because they’re not reversible. That being said, often we just treat the endocrine toxicity. If you look at the toxicities in general, large picture, the rates of immune-related adverse events, the need for high-dose steroids is about 30% with nivolumab-ipilimumab. It’s very similar in a lot of the IO-TKI combinations, anywhere from 20% to 30%.
So we’re dealing with immune-related adverse events in both IO-IO and IO-TKI. Overall with IO-IO it’s a bit simpler because when you have toxicity you know it’s the IO, and you can manage appropriately. When you have an IO-TKI, you have all of these overlapping toxicities like liver issues or diarrhea, so it’s a matter of holding the TKI and seeing how things go in that regard. But I think the biggest factor is, yes, there are those rare but significant toxicities with IO-IO, which I tell my patients about. Fortunately, they are very rare, and that’s likely why we see this marked difference in quality of life with nivolumab-ipilimumab vs sunitinib.
Elizabeth Wulff-Burchfield, MD: Those are so hard to counsel patients about. Just the unpredictability of IO therapies is such a difficult communication conundrum, at least for me. I’ll put in a little plug for the ATRIUM trial, which is looking at abatacept as an intervention for immune-mediated myocarditis. It’s already included as one of the options in the guidelines, but that trial is ongoing, and I hope people will open it and contribute to it because I think we need to know the answer to that.
Transcript edited for clarity.
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