S3604 Cabozantinib-Induced Acute Pancreatitis in a Patient With Metastatic Renal Cell Carcinoma

Introduction: Cabozantinib is a novel tyrosine kinase inhibitor used to target vascular endothelial growth factor receptor (VEGFR), MET and AXL in the treatment of metastatic renal cell carcinoma. It has been associated with gastrointestinal side effects, but rarely with acute pancreatitis. Below, we illustrate a rare case of symptomatic cabozantinib-induced acute pancreatitis that resolved with discontinuation of the drug and prolonged corticosteroid therapy. Case Description/Methods: A 61-year-old man with metastatic clear-cell renal carcinoma presented to the emergency department for a 4-day history of constant, severe epigastric abdominal pain radiating to his mid-back. His serum lipase was elevated to 262 U/L (>3× upper limit of normal), consistent with acute pancreatitis. His serum transaminases and bilirubin were within normal range. Magnetic resonance cholangiopancreatography (MRCP) did not reveal biliary etiology or choledocholithiasis; however, there was some peripancreatic effusion noted. He denied significant alcohol use; serum IgG4 and triglycerides were within normal limits. Notably, the patient has been on cabozantinib 20 mg daily which was reduced from 80 mg daily due to prior grade 1 dermatitis and grade 1 colitis with diarrhea. His abdominal pain improved upon discontinuing cabozantinib and management with intravenous fluids and opioid analgesia. Given the temporal association and exclusion of other etiologies, cabozantinib-induced pancreatitis was the leading diagnosis. Oral prednisone 1 mg/kg with a 12-week taper was initiated. Upon 3-month follow-up, the patient has not had any symptom recurrence, and repeat imaging demonstrated resolution of the peripancreatic effusion. He opted to withhold systemic therapy and is currently on active surveillance with regular follow-up. Discussion: Acute pancreatitis is a very rare adverse effect of cabozantinib, with <1% incidence noted in the METEOR randomized, open-label phase 3 clinical trial. Drug-induced pancreatitis is a diagnosis of exclusion with reasonable temporal association and improvement upon discontinuation of the offending agent. This case highlights the consideration of cabozantinib therapy as a potential etiology for patients with renal cell carcinoma who develop acute pancreatitis. Shared decision making must be utilized with patients in deciding whether to resume cabozantinib after completing corticosteroid therapy and symptom resolution.