Safety of denosumab in patients with refractory differentiated thyroid cancer and advanced medullary thyroid cancer.

Abstract

e17578 Background: Few data exist regarding the use of denosumab in patients with bone metastases from radioactive iodine (RAI) refractory differentiated thyroid cancer (DTC) and advanced medullary thyroid cancer (MTC). We aimed to describe adverse events of specific interest - osteonecrosis of the jaw (ONJ) and severe hypocalcemia - in this rare setting. Methods: We retrospectively reviewed the charts of all the patients treated with denosumab for bone metastases from RAI-refractory DTC and advanced MTC in our institution. All patients had a calcium measurement and a clinical and radiological dental screening before denosumab initiation. All patients without hypercalcemia received a calcium supplementation. We assessed associations between ONJ or severe hypocalcemia ( < 1.75mmol/L) and suspected risk factors by Fisher exact tests. Results: Between 2014 and 2018, 23 patients were treated with denosumab. Two-thirds of patients were male (n = 16), median age was 69 years (range 43-87). Histology was DTC and MTC in 19 (83%) and 4 (17%) patients, respectively. DTC patients had received a median cumulated dose (CD) of 300 mCi of RAI (range 100-700). Ten patients (43%) had at least one cervical surgery for recurrence or persistence, and 6 (26%) had cervical radiotherapy. Four patients had hypoparathyroidism before denosumab initiation. Two-thirds of patients ( n =15) received a tyrosine kinase inhibitor (TKI) in association with denosumab. The median duration of denosumab was 20 months (range 1-47). ONJ occurred in 6 patients (26%) and severe hypocalcemia in 3 patients (13%). Conclusions: Patients with RAI-refractory DTC and advanced MTC are at high risk of ONJ and severe hypocalcemia under denosumab treatment. Benefit/risk ratio should be highly weighted particularly when treatment is prolonged. Patients should be closely monitored for the risk of ONJ and hypocalcemia. [Table: see text]