Abstract: FR-PO268
FGFR Inhibitors in Cholangiocarcinoma and Urothelial Bladder Cancer Resulting in Hyperphosphatemia, Low Parathormone, and High Calcitriol: The Side Effects of FGF23 Blockade
Session Information
- Onconephrology: From AKI to CKD and Everything in Between
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1700 Onconephrology
Authors
- Brito, Germana Alves, ACCamargo Cancer Center, Sao Paulo, São Paulo, Brazil
- Pereira, Benedito J., ACCamargo Cancer Center, Sao Paulo, São Paulo, Brazil
- Baptista, Aline Lourenco, ACCamargo Cancer Center, Sao Paulo, São Paulo, Brazil
- Poluboiarinov, Maria de Nazaré Simão, ACCamargo Cancer Center, Sao Paulo, São Paulo, Brazil
- Moyses, Rosa M.A., Universidade de Sao Paulo Hospital das Clinicas, Sao Paulo, São Paulo, Brazil
Introduction
Hyperphosphatemia is the most frequent adverse event in patients treated with FGFR (fibroblast growth factor receptor) inhibitors. FGF23 and FGFR1 play key roles in phosphate homeostasis and hyperphosphatemia results from FGFR1 inhibition.
Case Description
Case series of patients with urothelial bladder cancer and cholangiocarcinoma (CCA) taking FGFR inhibitors (erdafitinib or futibatinib) at AC Camargo from July 2021 - February 2023. Creatinine, serum phosphate, parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25 vitD), 24h urinary phosphate level were measured after 4 weeks of therapy.
As described in the table below, we included 4 patients with cholangiocarcinoma and 2 with urothelial bladder cancer. Hyperphosphatemia occurred in 100% of the patients, with serum phosphate ranging from 6 to 7.5 mg/dl, accompanied by decreased urinary phosphate. PTH was suppressed in 2 of the patients, whereas high 1,25 vitD was seen in half of them. Hyperphosphatemia caused a temporary interruption of treatment, to control serum phosphate. Also, phosphate binders were administered to all patients. Acetozolamide was admistered to patients 3 and 4, but had no effect on serum phosphate and caused worsening of dry mouth and metabolic acidosis. Ungual lesions were present in all cases and eye toxicities, such as serous retinal detachment, were seen in 4.
Discussion
FGFR1 blockade caused by FGFR inhibitors is associated with hyperphosphatemia, hypophosphaturia, high 1,25 vitD and PTH suppression, as described in animal models of FGF23 blockade. The metabolic changes caused by these drugs are a undesirable, but important side effects that might limit their use in many patients affected by cancer with genetic alterations in FGFRs.
CCA = cholangiocarcinoma; P = Phosphate; iCa = Ionized Calcium; Creat = creatinine; 1,25 vitD = 1,25-dihydroxyvitamin D; n/a = not available