Therapeutic Approach for Metastatic Renal Cell Carcinoma - Episode 1

Case of Rapidly Progressing mRCC

April 23, 2018

Neeraj Agarwal, MD:So, this is a case of a 73-year-old, otherwise pretty healthy lady, who has a history of mild diabetes and diet control. She came with hematuria, fatigue, some weight loss—not very noticeable, but, upon questioning, she reported some weight loss. After a workup was finished, a CT scan of the abdomen showed a left kidney mass, approximately 5 cm in size. She had a left-sided radical nephrectomy, and it basically revealed a clear-cell type renal cell carcinoma, 5 cm in size, but it was invading the left renal vein. So, the patient was staged to have a T3N0M0 disease. There was no evidence of metastasis on CT scans or anywhere else, and she recovered pretty well from the surgery. And then she was seen again 3 months after. All the scans were negative, and she continued her follow-up for the next 9 months when she was found to have, on a routine surveillance scan, multiple new liver metastases. Her laboratory data were important for high calcium and anemia, and also because she had lost approximately 4 or 5 pounds of body weight.

So, looking at this patient who has now developed metastatic disease, if you look at the risk factors, she belongs to the intermediate- or the poor-risk category. She has a time of onset of metastasis—which is less than a year—she has high calcium, and she has anemia, so she belongs to the poor-risk category—although you can argue that if it was really a poor risk or if it was intermediate risk, but technically speaking following the IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) criteria, she belongs to the intermediate-risk category. Now she needs to start treatment because she has metastatic disease.

So, laboratory data revealed she had high calcium, but otherwise, they were pretty unremarkable. The patient was diagnosed to have intermediate-risk category disease because the time of onset of metastasis was within 1 year of original diagnosis and nephrectomy, and she had high calcium.

The laboratory data revealed she had high calcium, but other labs were pretty unremarkable. Given that she had an interval of less than 1 year between the original diagnosis of kidney cancer and nephrectomy, and also the metastatic disease and hypercalcemia, she belongs to or belonged to the intermediate-risk category, having had 2 of the IMDC risk factors. Now she needs to start treatment. She also had PD-L1—expression testing done on the tumor, and the tumor was PD-L1–negative—so the tumor did not express PD-L.

So, she also had PD-L1 testing done on the tumor, and she was not found to have a PD-L1—expressing tumor. The treatment that was chosen for her was cabozantinib at 60 mg daily. After 4 weeks of being on cabozantinib, she developed grade 2 diarrhea, and the cabozantinib doses were decreased to 40 mg per day.

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