Treatment for Frail or PD-L1-Positive mRCC

Neeraj Agarwal, MD:Would I use a different dose of cabozantinib in a frailer patient? I think so. If I’m seeing a 79-year-old frailer patient than the patient I just described, I think I would start with cabozantinib at 40 mg daily and maybe further decrease the dose as long as patient is responding. So, yes, I think decreasing the dose of cabozantinib is often a wise decision in patients where we think 60-mg daily dosing may cause excessive toxicities.

Would I make a different choice as far as treatment selection is concerned for a patient whose tumor is expressing PD-L at more than 1%? I think so. If I look at the data from the CheckMate-214 trial, almost 300-plus patients out of almost 1000 patients whose tumors were expressing PD-L1 at more than 1% had dramatic progression-free survival benefit compared with sunitinib. The PFS with the combination was 22 months compared with 5 months with sunitinib. So, given these data, I do not have any doubt that PD-L—expressing tumors or patients with PD-L–expressing tumors need treatment with ipilimumab/nivolumab combinations—without any question.

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