RCC Panel Discusses Treatment Response, Dosing, Patient Management, and More

A roundtable discussion, moderated by Brad McGregor, MD, focused on the latest data in RCC treatment and management, including data from the American Society of Clinical Oncology Genitourinary Cancers Symposium 2024. Dr. McGregor was joined by Rana McKay, MD; Elizabeth Wulff-Burchfield, MD; and Alan Tan, MD.

In the next segment of the roundtable series, the panel addressed different dosing scenarios and shared tips on how to counsel patients on their treatment.

Watch the next segment in this series.

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Dr. McGregor: There’s been so much advances. We have all these great trials, but I think trying to make sure we can keep patients on the agents that we’re prescribing is really critical. Alan, you alluded to this earlier that nivolumab/ipilimumab may not be for everyone because of different things.

How do you maintain dose intensity in these trials? What are some different things you think about in the clinic, if you choose nivolumab/ipilimumab to keep it going or nivolumab/cabozantinib or pembrolizumab?

Dr. Tan: With nivolumab/ipilimumab, it’s all about trying to get up to that 4 doses of that induction period. Cross your fingers that they don’t have that grade 3, grade 4 event, which if they do, it’s manageable and oftentimes if they do have that grade 3, grade 4 event, it’s oftentimes associated with efficacy. Eventually you’ll get that 3-month scan. If they’re responding, I think once they get back on the single-agent nivolumab, the turbulence has hopefully disappeared and they can maintain on single-agent, or PD-1.

As far as IO/TKI, I use a lot of cabozantinib/nivolumab. I think the fact that they start with the 40 mg instead of the 60 mg is key there because these patients oftentimes are able to tolerate it better than some of the other ones. With all of the TKIs, it’s going to be cumulative, so I tell these patients, even though you’re tolerating it now, maybe 8 weeks from now, 12 weeks from now, you’re going to hit a threshold.

Some of my patients have been on for so long at their personal threshold. There has studies about intermittent TKI; some people have taken breaks as long as 90 days, and it really hasn’t impacted survival. There’s the STAR trial and then the TIDE-A study that was presented at ESMO that’s showing that in some patients that might be feasible, but overall, I tell patients if you have to take some breaks to wash out that toxicity back to grade zero/grade 1, by all means. Or if you have a wedding coming up and you want to be at your best, your daughter’s wedding, I’m okay with that.

Dr. Wulff-Burchfield: I do think that, and I don’t have any prospective data about this, but I’m someone who really believes that comprehensive counseling of the patient to reassure them that communication is not going to undermine our enthusiasm for treating their cancer.

I certainly spend a lot of time talking to folks about the idea that number one, it’s not their job to know if some symptom they have, if it’s bothering them, it’s not their job to know if it’s from their treatment. That’s my job. I tell them, let us know and I will determine. I think people get analysis paralysis thinking was that my taco or is that my medicine? I’m not sure. I think just encouraging them. I tell patients if you have an unpleasant symptom that lasts more than 1 day, I need a call on day number 2, and I will help you figure it out because that gives us the opportunity to intervene earlier and hopefully allow us to re-challenge patients.

I think that helps. Also reassuring patients that even if we have to stop the ipilimumab component early that they can still derive significant clinical benefit. I think trying to just reassure them that we’re not going to take away all their treatment. We’re not going to abandon them just because they have side effects.

The earlier we know, the more we can help them. I think that has been the single most important intervention in my clinic practice.

Dr. McKay: I think setting expectations is key. I think the other thing too is the way that we came about the doses in the context of these studies is really how we dose chemotherapy. The FDA has a huge initiative for dose optimization, and I don’t necessarily think that continuing to escalate hitting the MPD and going 1 step below is really the right strategy for targeted therapy. As we’ve come to see, there’s been some studies that have been done with cabozantinib looking at different doses of cabozantinib and that actually efficacy is retained from a PFS standpoint even at different dose intensities.

I think we do have some work to do in that regard, but I think patient education, holidays, treatment breaks are all ways to actually maximize their time on treatment.

Dr. McGregor: If you look at all the studies, they picked a starting dose and that’s what the studies did. I tend to follow that starting dose. But if you look at the same studies, over half the patients in every single IO/TKI study had to dose reduce. I think it’s really important early on, you just have to set an expectation to get going. Most patients dose reduce, it didn’t compromise efficacy. If you can tolerate the higher dose, you should take it. But if you can’t, we shouldn’t. Because I want to keep going this long term. We don’t want to get into trouble by having to take something too long early on. Cause that may jeopardize our long-term care.