Clinical Rationale for TKI Choice in mRCC

Neeraj Agarwal, MD:In the CABOSUN trial, which was a phase II randomized trial of almost 160 patients comparing cabozantinib with sunitinib, cabozantinib was clearly superior to sunitinib in terms of progression-free survival, which was also confirmed by independent radiological assessment. The progression-free survival with cabozantinib was 8.6 months compared with 5.3 months for sunitinib. And this was a relatively high-risk patient population with only intermediate- and poor-risk patients being included, but—more notably—30% of patients had bone metastases. So, after confirming superiority of cabozantinib over sunitinib by an independent radiologic assessment, in my mind, cabozantinib is a drug of choice for this patient.

Going back to the question of sunitinib versus pazopanib, I did not choose pazopanib in this patient, because we already have data from the COMPARZ trial from a few years ago, where sunitinib was found to be equivalent to pazopanib or vice versa, as far as progression-free survival was concerned. So, we know that pazopanib and sunitinib are very comparable as far as progression-free survival is concerned, and cabozantinib is clearly superior to sunitinib from the CABOSUN trial. The extrapolation of the data basically leads me to believe that cabozantinib is also superior to pazopanib, with the caveat that these 2 drugs have not been compared head-to-head in a randomized clinical trial.

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