Risk factors in the management of advanced renal cell carcinoma

Robert J. Motzer, MD: When patients present with RCC [renal cell carcinoma], do you stratify and objectify a risk factor? How do you see this fitting into your management of CCR in your own practice?

Marie-Carlo, MD: The dilemma is that we have several diets that work quite well, so how do we choose. I agree with other people, and we were lucky enough to have early experience with this combination treatment when we were in the early phase trial and I am familiar with dose and dose adjustments. This is the most important thing when choosing one of these combinations. It’s one you know well, you know the dose adjustments and the side effects because as you can see from the data, even though they’re both anti-VEGF [vascular endothelial growth factor]there are differences between sunitinib [Sutent] and lenvatinib [Lenvima] and the others in terms of adverse effects. With sunitinib, we see more dysphonia. If I had a patient who is a singer, which I had, then you might want to choose a regimen where dysphonia is less of a risk. This diet is effective in all risk groups, so I am not selecting any particular diet. I discuss this type of diet with all risk groups, obviously intermediate and low risk. I also present the idea of ​​ipilimumab [Yervoy] and nivolumab [Opdivo] and discuss the pros and cons of each regimen with the patient. I have also been more aggressive towards patients with a history of mild autoimmune disease, always thinking of IO [immuno-oncology] therapy. For example, a few years ago, those patients were probably borderline for trial eligibility who had a history of colitis or psoriasis. In particular, our subspecialists have become very proficient with these agents and, as a preventive measure, I refer patients who, for example, had a possible diagnosis of Crohn’s disease to the gastroenterologist for evaluation and co-management. I have successfully treated a few patients with a history of mild autoimmune disease with IO. I use the help of my colleagues in different [departments]dermatologists, gastroenterologists, because as you said the benefit and overall survival is there and I want to make sure I evaluate everything before I don’t give them that option.

Robert J. Motzer, MD: We were one of the main recruiters for the CLEAR trial. One aspect of this program that really struck me was how effective it was. The fact that we still have patients who were treated in this trial, who are doing well in this program and are having a durable response, most of the patients required a dose reduction. In this study, the proportion of patients on lenvatinib/pembrolizumab [Keytruda] who had a dose reduction was around 60% and that’s part of the theme of lenvatinib is to start with a high dose for maximum efficacy and then reduce the dose needed for toxicities. Based on your own experience, are there certain patient populations that you think would be problematic to offer lenvatinib/pembrolizumab in addition to the autoimmune issue around lenvatinib in terms of different comorbid conditions that make you more away from each other’s lenvatinib/pembrolizumab programs?

Marie-Carlo, MD: Definitely hypertension. Even with optimal control, if someone is hypertensive to begin with, we look at diets, we preemptively increase their blood pressure medications and they can still get quite hypertensive with that and that would be a population that I would be cautious about offering that. Certainly if they’ve had a recent cardiac event or stroke I stay clear of those GI issues that would put them at risk of perforation that’s another population I would stay away from anti-VEGF until at least we get a better disease response. I don’t know if you have other patients?

Robert J. Motzer, MD: The predominant early adverse event is hypertension. I completely agree with you. If a patient has uncontrolled hypertension, I would certainly encourage another regimen. Especially if there are people who have a low intermediate risk, that would be an ideal candidate for ipilimumab/nivolumab. For the patients I offer lenvatinib/pembrolizumab to, I want to make sure their blood pressure is well controlled before starting the regimen and I always advise them that this is an adverse event that could occur early in a few days and provide them with metrics and ask them to get a blood pressure cuff and take blood pressure at home and call us if there is any worsening or development of hypertension. This is when patients need advice.

Marie-Carlo, MD: Regarding the first question, we start patients on both drugs on the same day. They come to the clinic, they get training, and then I like to see the patients 2 or 3 weeks later. If not me, then a nurse practitioner or a physician assistant. I ask patients to monitor their blood pressure daily at home, and we give them parameters, 140/90 or something to call and let us know if there’s any kind of these constant BPs [blood pressure] higher readings. I agree, blood pressure, maybe some mucositis and some diarrhea may be more difficult on this diet. I would say that I don’t really like in the early stages going more than 2-3 weeks without seeing a patient. And that’s also why I’m starting pembrolizumab on the 3 week dose, so we can have an integrated check every 3 weeks. But of course, over the phone, try to do it more frequently.

Transcript edited for clarity.

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