Incidence of hypocalcemia in patients with castration-resistant prostate cancer treated with denosumab: Data from a non-inferiority phase III trial assessing prevention of symptomatic skeletal events (SSE) with denosumab administered every four weeks (q4w) versus every 12 weeks (q12w)—SAKK 96/12 (REDUSE)

139 Background: DN given q4w has shown superiority in delaying skeletal related events over q4w zoledronic acid (ZA). Recently it has been demonstrated that ZA q12w is non-inferior to ZA q4w. The objective of REDUSE is to show non-inferiority for DN q12w versus q4w in terms of SSE. Here we present an interim analysis for the secondary endpoint HC. Methods: Patients (pts) with castration resistant prostate cancer (planned N=690) were randomized 1:1 to DN q4w (Arm A) vs q12w (Arm B) after a 16 week induction phase with application q4w. All pts received vitamin D (ViD) 400 U and calcium (Ca) 500 mg daily. Measurement of corrected serum-Ca was mandatory before each DN injection. This interim analysis was performed after 3.5 years of accrual. Men who received ≥ 1 dose of DN were considered evaluable. Results: 383 pts were evaluable. HC occurred in 28.7% during the first 16 weeks (DN q4w for all pts) and 30.2% afterwards. After the induction phase HC occurred in 40.2% in Arm A and in 20.3% in Arm B. Grade 3 (2.1%) and 4 (1.1%) HC were rare, most frequently occurring in the first 16 weeks. After 1 year of treatment, the incidence of HC was lower in both arms (A: 30.8%, B: 18.7%). A clinically relevant difference for HC was noted between the two arms after the induction phase (table). Conclusions: In our trial nearly 30% of all men treated with DN experienced HC in the q4w induction phase despite mandatory supplementation of calcium and ViD and measurement of Ca. This rate was considerably higher than reported in the registration trials of DN (13%). After induction treatment the incidence of HC is considerably lower in the q12w arm compared to q4w. This suggests that DN given q12w has a more favorable long time toxicity profile (HC) compared to DN q4w. Change in HC grade after week 16 (week 1 – 12: DN q4w Arm A+B), thereafter q4w in Arm A and q12w in Arm B. Clinical trial information: NCT02051218. [Table: see text]