Case Details and Initial Impressions

Daniel J. George, MD: This case involves a 48-year-old gentleman who presented to his local physician complaining of some back pain and some right flank pain. He was found, on evaluation with a CT scan, to have a large right renal cell renal mass, as well as significant retroperitoneal adenopathy and evidence of a mass on his left adrenal gland, as well as a lytic lesion in his T9 vertebral body. This is very suspicious for renal cell carcinoma on presentation at stage IV metastatic. Because of the presence of the lytic lesion in his T9 vertebral body, palliative radiation therapy was performed first, after a biopsy confirmation of the renal cell carcinoma.

Following palliative radiation to his spine, the patient underwent a debulking nephrectomy, removing his renal tumor out of his kidney, as well as multiple lymph nodes. Pathology from this revealed clear-cell carcinoma consistent with a renal cell carcinoma primary and a stage IV metastasis. The patient subsequently recovered from his surgery and was put on pazopanib 800 mg once daily. He tolerated this pretty well at first. He had some fatigue, some moderate degree of diarrhea that was initially controlled with antidiarrheal medication, and demonstrated evidence of a disease reduction in his remaining adenopathy and adrenal gland. He started this therapy in 2014 and was on it for over 1 year, over which time he continued to have stable disease. However, over this period of time, fatigue built up—as we commonly see—and episodes of diarrhea resulted in some increased weight loss and worsening fatigue, resulting in a dose reduction down to 600 mg. The patient continued to have evidence of overall stable disease, but slow increase in his tumor burden, particularly in his adrenal gland.

Then, about in the spring of 2016, he started developing increasing back pain. Workup revealed evidence of disease progression in his T9 lesion that had previously been radiated, as well as other spots in his spine, suggestive of worsening metastatic disease. At that point in time, the patient was switched from pazopanib to cabozantinib 60 mg once daily.

This case, if I can just comment, I think is atypical in that this is a young patient, 48 years old, but typical in that this patient had evidence of a disease that had spread to multiple organs and, therefore, was what we consider to be in an intermediate risk of presentation up front. His response to pazopanib was really exceptional: over 1 year of disease control even with a dose reduction. So, this was really suggesting, despite the intermediate-risk features, a robust dependence of that tumor on the VEGF pathway.

Case Scenario 1: A 50-year old male with relapse of metastatic RCC

January 2014

• A 48-year old Caucasian man presented to his physician complaining of right upper quadrant discomfort and back pain
• CT scan of the abdomen and pelvis showed a large right renal mass with retroperitoneal adenopathy, largest node measuring 2.5 cm on right axis; metastatic lesion to T9, lytic
• The patient underwent cytoreductive nephrectomy, retroperitoneal node biopsy
• He was diagnosed with stage IV renal cell carcinoma, clear-cell histology, with metastases to bone and contralateral adrenal gland
• After radiation therapy to T8, he was then started on pazopanib 800 mg
• The first follow up scan showed a decrease in size of the adrenal lymph node
• The patient reported moderate diarrhea and mild fatigue which was controlled with antidiarrheal medication and rest
• He continues to do well with improved tolerance after dose adjustment to 600 mg

April 2016

• Imaging shows slow but steady progression in the adrenal lesion
• The patient complains of increasing back pain. He reports nausea and
• Pazopanib was discontinued and the patient was started on cabozantinib 60 mg