Participants Discuss Differences in Treatment in First-Line mRCC

Daniel J. George, MD (Moderator)

Eleanor Easley Distinguished Professor in the School of Medicine

Professor of Medicine, Medicine

Professor in Surgery

Duke Cancer Center

Durham, NC

CASE SUMMARY

• A 59-year-old African-American woman was diagnosed with a left renal mass.
• She underwent left radical nephrectomy in December 2019.
  • Clear cell renal cell carcinoma (RCC)
  • T3aN0Mx, International Society of Urological Pathology grade 3
• Nine months later, she reported pain in hips and left chest.
• Radiographic diagnosis: stage IV RCC, with osteolytic lesions in iliac crest and left fifth rib
• ECOG performance status: 1
• Laboratory results:
  • Hemoglobin: 11.1 g/dL
  • Elevated liver function tests
  • Mild hypercalcemia (10.8 mg/dL)
  • Neutrophils, platelets: within normal limits
• The patient received nivolumab (Opdivo) plus ipilimumab (Yervoy).

DISCUSSION QUESTIONS

• In immune checkpoint inhibitor (ICI)-based combination regimens for intermediate/poor-risk metastatic renal cell carcinoma (mRCC), what differentiators come to mind? ​
  • Specific disease characteristics (eg, tumor velocity, nature of metastasis, presence of sarcomatoid features)​
  • Patient (eg, frailty/performance status, symptoms, comorbidities)​
  • Other characteristics
• Based on your own experience, how does the efficacy and safety profile of ipilimumab/nivolumab (Opdivo) compare with ICI-tyrosine kinase inhibitor (TKI) regimens for intermediate/poor-risk mRCC?

Joanna Metzner-Sadurski, MD: I was with Dr Louay Hannah once, and I like what he said, that he likes ipilimumab/nivolumab, because this is the only regimen which potentially can cure patients. That's really what we want. I don't know if we can say cure, but there are long-term survivors [with mRCC].

I like ipilimumab/nivolumab, but if I have a patient who is crashing and they’re a younger patient, I will choose lenvatinib [Lenvima]/pembrolizumab [Keytruda] because I want to have a quick response. They might not live long enough to get ipilimumab/nivolumab response, so for a faster response, I choose on lenvatinib/pembrolizumab. If the patient has sarcomatoid features, I will definitely choose ipilimumab/nivolumab.

Daniel J. George, MD:That’s a good point; the tumor characteristics, the pace, the burden of disease, and the symptoms. I’ve had patients I haven't even been able to treat because they're so sick and have so much disease, you can't get them out of the hospital. It’s very difficult. For the patients that are just out of the hospital, but they still have a huge tumor burden, I agree with that. We've done that particularly with brain or spine metastases and steroid use; they've done great on lenvatinib/pembrolizumab and cabozantinib [Cabometyx]/nivolumab. I agree with that approach.

How about the patient characteristics, [things like] age, frailty, and performance status? Are there certain populations you won't treat with ipilimumab/nivolumab, or you won't treat with TKI-IO based on the patient characteristics?

Michael M. Goodman, MD: In somebody who has severe cardiac disease or something like that, I wouldn't use a TKI. But, in general, [I would use] ipilimumab/nivolumab, unless there's a strong reason not to give it, is generally my practice.

George: I agree with that. I would say renal disease, liver disease, and another couple that I worry about with the TKIs because of toxicity. Everything is a little risky in those patients. Heart disease, renal disease, liver disease, it's still a risk with ipilimumab/nivolumab, but it's a low risk. It could happen. You could get a hepatitis on top of that liver disease, or cardiomyopathy or something, but it's rare.

With TKIs, you feel like even a little bit of toxicity could tip them over, and I agree with that. These are always difficult [diseases] to manage. The other thing is, you don't necessarily have to get through 4 cycles to get a benefit. You might be able to stretch it out a little bit and get through 3 cycles and still get [response].

We've studied some alternative regimens with ipilimumab/nivolumab and every-8-weeks ipilimumab. It’s probably not quite as effective, but still has some efficacy. For these patients, when you're nervous, you maybe have a little more flexibility with the IOs. If you can't give a TKI every 8 weeks, you have to adjust in the real world around that.