Patient Profile 1: Intermediate/Poor Risk RCC Treated With Ipilimumab-Nivolumab


Experts review a clinical scenario of intermediate- and poor-risk renal cell carcinoma that is managed with ipilimumab-nivolumab and nivolumab maintenance.

Robert J. Motzer, MD:
I am Robert Motzer, the kidney cancer section head and the Jack and Dorothy Byrne Chair in Clinical Oncology at Memorial Sloan Kettering Cancer Center in New York, New York. I’m joined by my institutional colleagues Dr Chung-Han Lee and Dr Maria Carlo. I’d like to invite them to introduce themselves.

Chung-Han Lee, MD: I’m Dr Chung-Han Lee. I’m a medical oncologist at Memorial Sloan Kettering Cancer Center. I currently specialize in various RCC [renal cell carcinoma] clinical trials.

Maria I. Carlo, MD:My name is Maria Carlo. I’m a medical oncologist as well. I specialize in clinical genetics, especially of GU [genitourinary] cancers.

Robert J. Motzer, MD: Welcome, and thanks for joining me. We’re going to discuss recent advances in the treatment of renal cell carcinoma and their impact on clinical practice. We’ll present real-world patient cases and discuss our treatment approach to illustrate how we incorporate recent data into practice to manage patients with renal cell carcinoma. Let’s get started on our first topic.

Chung-Han Lee, MD: For our first case we have a 57-year-old man, a former smoker with a past medical history of significant asthma hypertension who initially presented with fatigue and abdominal pain. A CT of his chest, abdomen, and pelvis showed some sub-centimeter pulmonary nodules and small lymph nodes in the mediastinum. He did have a sizable 12.5-cm perihepatic mass with some surrounding smaller perihepatic lesions there. We end up doing a CT-guided biopsy of the perihepatic mass, which came back as clear cell renal cell carcinoma with sarcomatoid features.

You can see some representative images from his baseline, and you can see the 12-cm mass on the right-hand side and then further up, 1 of the perihepatic lesions. A decision was made to start the patient on the combination of ipilimumab plus nivolumab at the FDA-approved dose of 1 mg/kg of ipilimumab and 3 mg/kg of nivolumab. However, after his first dose of ipilimumab-nivolumab he did develop a rash. Here, you can see some representative images of the full-body rash he ended up developing, which was quite pruritic. We started him on prednisone 0.5 mg/kg with rapid improvement on his rash. After his steroid taper, he had complete resolution of symptoms. A decision was made to start him on nivolumab maintenance therapy at the FDA-approved dosage of 480 mg every 4 weeks as maintenance therapy.

Here, you can see the patient develop a fairly good clinical and radiographic response to systemic therapy with near resolution of the perihepatic mass that we see on the right in just a few months.

Robert J. Motzer, MD: That’s a great case, illustrating our management with I/O [immuno-oncology] combination therapy for clear cell carcinoma. When you’re approaching patients in clinic, how do you decide on how do you prognosticate them into the risk for determining treatment?

Chung-Han Lee, MD: The first step in making that clinical decision is looking at risk stratification for the patient. This was a young patient who presented with de novo metastatic disease. There was no evidence of any treatment. He was free interval, so at a minimum he would be intermediate-risk disease. For him, his laboratory values were stable and otherwise healthy. The main question in my mind is about varying treatment approaches and which 1 to select. For him, the sarcomatoid features did sway me a little more toward thinking about doing it ipilimumab-nivolumab up front as the systemic therapy, especially given his young age.

Robert J. Motzer, MD: What’s been your experience with the tolerability of the ipilimumab-nivolumab? This patient had a rash. What’s been your experience in terms of the main adverse events to look for and how you manage them with ipilimumab-nivolumab?

Chung-Han Lee, MD: Generally, my experience with the tolerability of ipilimumab-nivolumab remains fairly good, though the potential of I/O toxicities remains very unpredictable. This is 1 that I will tell patients in advance, that even though it’s not common to develop an I/O–related toxicity, they can certainly be quite dramatic when they occur. The potential adverse effects that I discuss with the patient in advance is the risk for autoimmune colitis, autoimmune hepatitis, even pneumonitis or cardiomyositis related to the medications. I also bring up that on occasion people can develop things like hypothyroidism or adrenal insufficiency. For this patient, the occurrence of a dramatic rash is less common. But for most of these adverse effects, there may be a requirement for steroids afterward. But most patients will end up coming off the steroids and still do reasonably well after the steroid taper.

Robert J. Motzer, MD: Maria, in terms of options for this patient, Joe treated him with ipilimumab-nivolumab. What are some other options in terms of programs you could also offer this patient based on the recent studies? How would you choose 1 or the other?

Maria I. Carlo, MD: It would be reasonable to offer this patient a combination of anti-VEGF and immunotherapy because he’s at least intermediate risk. For all risk groups, immunotherapy and anti-VEGF is reasonable. Which 1 to choose of the 3 that are FDA approved? As the studies have evolved, I tend to use them more frequently because I’m familiar with the drugs. But all 3—axitinib, pembrolizumab-lenvatinib, and pembrolizumab or cabozantinib and nivolumab—would be fair options. In this scenario, I tend to agree with Joe that nivolumab and ipilimumab is a good option for the patient, especially because there’s no lesion right now. That’s impending doom like a lesion in the spinal cord, for example. That would sway me away from ipilimumab-nivolumab because I am looking for a higher, quicker response rate, which the trials have shown with the anti-VEGF–TKI [tyrosine kinase inhibitor] combinations. In this case—the absence of a lesion that’s going to cause imminent impairment, the fact that he’s young, and the sarcomatoid features—I would have made the same choice of ipilimumab-nivolumab.

Robert J. Motzer, MD: The point on the sarcomatoid features is a good 1. Joe did the sarcomatoid features impact on your decision. In what way for this patient?

Chung-Han Lee, MD: The sarcoma features definitely did impact me and thinking about the patients. Historically speaking, we’ve seen less of a clinical response to at least single-agent TKIs when sarcomatoid features were present. Most of the data with the I/O combinations have shown increased levels of activity related to the sarcomatoid features. That part of the histology did sway me toward a more I/O–based approach for him.

Transcript edited for clarity.

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