Thyroid dysfunction from inhibitor of fibroblast growth factor receptor

Background: Thyroid dysfunction has not been previously reported in clinical trials of selective fibroblast growth factor receptor (FGFR) inhibitors including AZD4547. Herein, we report a case of worsening hypothyroidism in a patient with advanced urothelial cancer treated with AZD4547. Case presentation: An 80-year-old Caucasian female with metastatic urothelial carcinoma failed first-line chemotherapy with gemcitabine and carboplatin and second-line treatment with atezolizumab, an inhibitor of programmed cell death ligand 1. She developed hypothyroidism at completion of atezolizumab treatment and responded to levothyroxine. Subsequently she was enrolled to a phase II study and received AZD4547 due to an actionable mutation at FGFR3 found in tumor biopsy. Two months later, she experienced recurrent hypothyroidism symptoms, and was hospitalized twice for small bowel obstruction. Her thyroid stimulating hormone level was significantly increased to 2957 uIU/mL (reference range 0.8-7.7 uIU/mL). Her levothyroxine dose was increased accordingly. Her thyroid function returned to normal 1 month afterwards, and small bowel obstruction did not recur. Conclusion: Further reports and studies will be needed to confirm the relationship between AZD4547 and hypothyroidism. Based on this observation and possible mechanisms for thyroid dysfunction discussed in this paper, routine thyroid function monitoring in patients receiving FGFR inhibitor should be considered.