TKI Therapy Versus I-O Therapy in mRCC

Neeraj Agarwal, MD:What is the rationale for choosing cabozantinib over the ipilimumab/nivolumab combination in this patient? So, first of all, the ipilimumab/nivolumab combination is not available. It’s not FDA approved. Moving forward 2 months or 3 months, assuming this combination is approved, I still think cabozantinib would be a better choice in this given patient because the PD-L expression of the tumor was less than 1%. And if we look at the CheckMate-214 trial data, the progression-free survival was not experienced by those patients whose tumor did not express PD-L1. So, in my view, for this given patient, cabozantinib would be a better choice.

So, regarding safety and toxicity of cabozantinib versus the ipilimumab/nivolumab combination, I think these drugs are very different with their own safety and toxicity profile. Cabozantinib is a very traditional VEGF TKI, which also targets AXL and MET. And accordingly, we see toxicities more in line with VEGF TKIs, such as hand-foot syndrome, hypertension, fatigue, diarrhea, and so on. On the other hand, the ipilimumab/nivolumab combination is a very novel combination. It is an already established combination in metastatic melanoma, but for GU oncologists, it’s a very novel combination with its own novel set of side effects and safety profile. Safety toxicity profile of the nivolumab/ipilimumab combination is very different from a TKI like cabozantinib. We are mainly talking about autoimmune side effects. So, if we look at the CheckMate-214 trial, 60% of patients required frequent treatment with corticosteroids, which is, in my view, a relatively higher use of steroids, more than I have practiced in my clinic with single-agent nivolumab.

Transcript edited for clarity.

Case Scenario: A 73-year old female with rapidly progressing mRCC

March 2017

• A 73-year old woman with clear cell RCC, hyperlipidemia, and type 2 diabetes, which are both managed medically
• Her baseline patient and disease characteristics were:
  • ECOG PS 0, KPS 90
  • pT3bNxM0 (AJCC stage 3)
  • 5-cm left kidney tumor mass with extension into the left renal vein
• She underwent radical nephrectomy within 1 month following diagnosis

December 2017

• The patient reported loss of appetite and weight loss
• CT imaging showed multiple liver lesions, 2 small nodules in the right lung upper lobe, and mediastinal lymphadenopathy
• Laboratory findings notable for Ca2+ 14.8 mg/dL
• PD-L1 expression, <1%
• Remarks: RCC disease progression; IMDC risk stratification, intermediate
• The patient was started on cabozantinib, 60 mg daily
• After 4 weeks on therapy she developed grade 2 diarrhea and her dose was reduced to 40 mg