Incidence of osteonecrosis of the jaw in patients receiving denosumab or zoledronic acid for bone metastases from solid tumors or multiple myeloma: Results from three phase III trials.

Abstract

9640 Background: In patients with metastatic bone disease (MBD), the use of antiresorptive therapies such as denosumab or zoledronic acid (ZA) reduces the risk of skeletal-related events but is associated with a small risk of osteonecrosis of the jaw (ONJ). Two phase 3 clinical trials of denosumab vs ZA in patients with MBD showed overall cumulative ONJ incidences to be 3.8% to 4.7% at approximately 5 years of treatment with denosumab across blinded and open-label extension phases. ONJ associated with ZA was only assessed in the blinded treatment phases, as patients switched to denosumab once superior efficacy was demonstrated. Here we report incidence rates of ONJ by first vs subsequent years of exposure for the blinded treatment phase of all three phase III clinical trials. Methods: Patients (n = 5,677) with bone metastases from solid tumors or multiple myeloma received either SC denosumab 120 mg and IV placebo or IV ZA 4 mg (adjusted for renal function) and SC placebo Q4W in the double-blinded treatment phase of each trial. Patients who received ≥ 1 active dose during the blinded treatment phase were included in this analysis for up to 44.5 months of denosumab exposure and 41.3 months of ZA exposure. Oral assessments were conducted at baseline and every 6 months thereafter by the investigator or other qualified examiner. Potential ONJ events were independently adjudicated by a blinded committee of experts. Results: The median (Q1, Q3) time to onset of ONJ was similar in both treatment groups (15.6 [9.5, 20.0] months for denosumab, 15.8 [11.0, 23.6] months for ZA). Cumulative incidence rates of ONJ during the blinded treatment phases for all three trials by patient-years of follow-up are shown below (Table). Conclusions: The incidence of ONJ increased with longer duration of antiresorptive exposure. There were no significant differences between treatment groups in ONJ incidence at year 1 or beyond. Clinical trial information: NCT00321464; NCT00330759; NCT00321620. [Table: see text]