Treatment Goals in Newly Diagnosed mRCC

Daniel George, MD:When I’m looking at a patient with intermediate-risk metastatic kidney cancer, I’m looking at their patient factors, individual factors, a lot. I’m looking at some tumor factors. And then, of course, we’re looking at the data. And when I look at CABOSUN data, that points me toward using cabozantinib in a patient like we presented, today.

But suppose, for instance, that this patient had a different course. Suppose that he presented with his left kidney tumor, and that it was resected with no lytic lesions. Three years later, suppose that the patient developed lung-only nodules. That patient would then be considered a good risk patient. If those were largely asymptomatic, without laboratory values, or abnormalities, we’d consider him a good risk patient. For me, that’s a patient in whom it is still the standard of care to use sunitinib or pazopanib. Historically, for the last 10 years, that’s been our standard of care. Many of these patients have done well with that. When we look at the CheckMate-214 data, the sunitinib control arm in the good risk patients really held up very, very well.

There are side effects that still need to be managed. Many of these patients can be on therapy for months or even years. It’s important to recognize this—when getting therapy, the patient can’t just sort of make it through the next 4 weeks. The patient needs to make it through cycle after cycle. This sometimes requires some significant changes. We’ll use different regimens with a drug like sunitinib—a 2:1 regimen. With pazopanib, we may lower that down. We may intermittently hold it, on occasion. With cabozantinib, it’s label is broad. The reality is, we’re able to use a drug like that, even in those settings. There’s evidence to suggest that in patients with good performance status, and patients without bone metastases, or in patients with low-volume disease, they all respond really well to cabozantinib. They respond even better than with sunitinib, from the CABOSUN study.

So, even though we don’t have direct evidence for using an agent like that in a good risk patient, you’re not wrong to do that. Use the TKIs that you’re comfortable or familiar with. Recognize the signs and symptoms. Work on helping these patients maintain a livable dose. For good risk disease, we don’t have to be at the MTD, for most of these patients. And for many of these patients, we can actually do deferred therapy. We don’t talk about it. It’s not necessarily something that there’s a lot of literature on. But, we’ve done a large registry, and we found that there’s a fair number of practitioners who will defer systemic therapy in patients with good risk, low-volume disease.

This almost goes in line with intermittent therapy—starting out with an observation, and then starting with therapy, and then maybe holding it, at some point, for side effects. And then, restarting that. Again, we don’t have a ton of data on this. But in practices like mine and my colleagues around the country, we’ll do these kinds of things in order to maintain the best quality of life/disease control balance.

So, looking at our case—our 52-year-old gentleman who underwent nephrectomy with progression of disease, who had some bone metastases that were radiated, and some lung nodules—you know it wouldn’t be wrong, if it’s FDA approved in the near future, to use a combination like nivolumab/ipilimumab. He’s 52 years old. He’s young. His tumor burden is not particularly high. This is the kind of patient in whom we might be able to achieve a complete response. We saw that in 9% of the patients in CheckMate-214. To me, that’s a fantastic goal, for many of our patients. Something that they’re looking forward to is getting the long-term disease control, whether that be a partial response (PR) or even complete response. So, that would be the rationale to starting with a strategy like that.

In addition, although it’s a little bit tough upfront, with the combination of 2 drugs, that’s a regimen that, after 3 months, we’re on what we’d consider to be kind of a maintenance therapy of just nivolumab, alone. That’s really attractive. In the future, we’re going to see opportunities to modify that dosing to every 4 weeks, or strategies that look at more chronic dosing, for patients that could potentially be on therapy for years. One of the questions that I think we’re going to struggle with is, do they need to be on therapy for that long? Before we answer that question, I think the most important questions are: who are the patients that need to start on this therapy? How do we get them through that 3-month induction period? And, when we get to a complete response or near PR, can we stop, or not?

Those are good problems to have. I struggle with that, a lot, in my practice. Right now, the big concern is making sure that these patients really optimize their outcomes with this regimen.

Transcript edited for clarity.

Case Scenario: A 52-year old male with mRCC

February 2018

• A 52-year old Caucasian man presented to his physician complaining of severe left-sided back pain
• Laboratory findings: mild anemia, otherwise WNL
• CT scan of the abdomen and pelvis showed a large left renal mass, several small lytic lesions in the lumbar and thoracic vertebrae, and a small pulmonary nodule
• The patient underwent cytoreductive nephrectomy
• Diagnosis; stage IV clear-cell renal cell carcinoma; good-risk
• He received radiation therapy to his spinal lesions and was then started on cabozantinib 60 mg daily
• The patient reported moderate nausea and vomiting and diarrhea after 6 weeks on therapy; he continues to do well with improved tolerance after dose adjustment to 40 mg
• Imaging at 3 months showed a significant decrease in size of the pulmonary nodule