Other Trials and Combinations to Treat Renal Cell Carcinoma

I think these are active agents. They’re important agents in our armamentarium for treating renal cell carcinoma, and I think as you look at the future, we’re going to be looking at these agents more in combination with immunotherapy [I/O], after immune therapy regimens, or potentially after other combinations.

Obviously, I think at this point we have a lot of great options at the front and center. We have cabozantinib for those who are unable to receive immunotherapy, and then we have nivolumab/ipilimumab, the combination of pembrolizumab with axitinib, and avelumab with axitinib. There’s always this debate over given there’s this multitude of options available, do I choose the combination of nivolumab with ipilimumab or do I choose a VEGF-I/O combination? There are lots of debates about which option is better for which patient. I think 1 trial we’re really excited about is the idea of using the combination of nivolumab and ipilimumab but actually adding cabozantinib to that regimen.

There’s a randomized phase III trial open for those patients with intermediate- and poor-risk disease where everyone receives the combination, nivolumab and ipilimumab, and then patients are randomized to either receive cabozantinib at a dose of 40 mg daily or placebo. And so I think that will be really exciting data that will hopefully help shape frontline therapy. And then I think obviously, that’s great, but there are patients who don’t respond to initial therapies, and so evolving that field. We’ve heard some data on the combination of pembrolizumab with lenvatinib following immunotherapy with or without VEGF, which has been very exciting.

And then we await the trials that are accruing right now, frontline trials looking at nivolumab and cabozantinib or sunitinib as well as combination, a trial looking at pembrolizumab with lenvatinib versus lenvatinib with everolimus versus sunitinib. So there are lots of exciting data, and I think that therapy for renal cell carcinoma continues to evolve as we get new trials and new data presented.

Transcript edited for clarity.

Case: A 70-Year-Old Man with Intermediate-Risk RCC

A 70-year-old Caucasian man presented to ER complaining of blood in his urine and abdominal pain.

H & P

• History of ulcerative colitis, controlled hypertension, and controlled hypercholesterolemia
• Lower back tender to touch

Labs

• CBC: Hgb 12.5 g/dL, HCT, PLT, WBC all WNL
• BP: WNL
• Lipid panel: WNL

Imaging

• Bone CT scan of the chest, abdomen, and pelvis showed a bilateral renal mass, a small lytic lesion in the lumbar vertebrae, several pulmonary nodules, and mediastinal and right hilar lymphadenopathy.
• Diagnosis: stage IV clear-cell renal cell carcinoma; intermediate-risk

Treatment

• Received cytoreductive nephrectomy
• He was started on cabozantinib 60 mg daily

Follow-up

• At 3 weeks of therapy patient tolerated treatment well, with mild fatigue and diarrhea, HTN remains controlled; blood in urine and lower back pain resolved; ECOG 0
• At 6 weeks of therapy the patient shows PR and reduction in size of the renal masses and lymphadenopathy.