Sequencing Therapy for mRCC Progression

Neeraj Agarwal, MD:What do I do when this patient experiences disease progression on cabozantinib? I think I base my decision or therapy selection for the second line, when second-line therapy is concerned, on the volume of disease or rapidity of disease progression. If the disease is progressing mildly—the pace is slow, indolent—I would choose nivolumab, because then I’m not really worried about not experiencing a progression-free survival benefit with nivolumab.

On the other hand, if this disease is rapidly progressing with multiple new lesions, including liver lesions, on cabozantinib, I would choose the lenvatinib/everolimus combination, because that combination has been shown to have remarkably high rates of objective response, which have not been seen by any other monotherapy so far in metastatic renal cell carcinoma.

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