An updated analysis evaluating skeletal related events (SREs) in CTRIAL-IE 13-21: Phase II trial of radium-223 (R223) in combination with enzalutamide (ENZA) for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

Abstract

215 Background: This phase II single arm study, previously reported on the safety and tolerability of the combination of R223 and ENZA in pts with mCRPC. R223 in combination with ENZA was well tolerated with acceptable safety and toxicity profiles. Methods: This study enrolled pts with mCRPC to bone with or without visceral/lymph node involvement progressing on ADT. Pts received 6 cycles of R223 (55 kBq/kg IV Q4W) in combination with ENZA (160mg/day), followed by ENZA alone. Bone health agents were initiated as per treating clinician choice. SREs were defined as: a pathologic fracture, spinal cord compression (SCC), necessity for external beam radiation (EBRT) or surgery to bone. SREs during the combination period and after completion of R223 are reported here. An unplanned retrospective analysis of all scans performed on each patient for any fracture was performed and is included. Results: From July 2015 to July 2017, 45 pts were enrolled. 42 pts (93.3%) received all 6 cycles of combination therapy. 16 pts (35.5%) remain on ENZA alone. In total, 6 pts (13.3%) had SREs. 4 developed pathological fractures (femur = 1, vertebrae = 3) while 3 had EBRT for pain. Of these 6 pts, 2 developed SCC requiring EBRT. The average time from starting R223 to SRE was 615 days. 2/6 pts were not receiving bone protection. One pt who developed a pathological fracture has subsequently died related to progressive disease (time to death = 292 days). In the retrospective analysis, 4 pts (8.8%) developed fractures which were associated with a history of trauma (radius = 1, tibia = 1 ribs = 2). 11 pts (24.4%) developed asymptomatic insufficiency fractures (ankle = 1, femur = 1, sacrum = 2, vertebrae = 4, ribs = 4). The average time to insufficiency fracture was 354 days. No interventions were required. The majority of pts (75.5%) on the study were receiving bone health agents. Conclusions: SREs were in keeping with previously published data. In an unplanned retrospective analysis, there was a higher incidence of asymptomatic insufficiency fractures in this cohort of patients, however no interventions were required. Clinical trial information: NCT02225704.