Adjuvant zoledronic acid reduces fractures in breast cancer patients; an AZURE (BIG 01/04) study.
Wilson C., Bell R., Hinsley S., Marshall H., Brown J., Cameron D., Dodwell D., Coleman R.
The fracture impact of adjuvant bisphosphonates in breast cancer is not defined with most trials reporting changes in bone mineral density as a surrogate. The AZURE trial (ISRCTN79831382) evaluated the impact of adjuvant zoledronic acid (ZOL) on fractures. The AZURE trial is an academic, multi-centre, randomised phase III study evaluating the addition of ZOL 4 mg to standard therapy (neo/adjuvant chemotherapy and/or endocrine therapy) for 5 years (administered by intravenous (iv) infusion every 3-4 weeks for 6 doses, then 3 monthly × 8 and 6 monthly × 5) in patients with stage II/III early breast cancer. Fracture data collected as part of skeletal-related adverse event reporting were analysed after a median of 84.2 months of follow-up and 966 disease-free survival (DFS) events. We assessed number of fractures, time-to-first fracture and the incidence of fractures before and after disease recurrence. Two hundred forty-four patients reported ≥1 fracture, 140 (8.3%) in the control arm (171 fractures) and 104 (6.2%) in the ZOL arm (120 fractures). Of the 291 fractures reported, 207 fractures occurred in the absence of recurrence (control 111, ZOL 96), 80 after recurrence (control 59, ZOL 21). The 5-year fracture rate was reduced from 5.9% (95%CI 4.8, 7.1%; control) to 3.8% (95%CI 2.9, 4.7%) with ZOL. ZOL significantly increased time-to-first fracture (HR 0.69, 95%CI 0.53-0.90; P = 0.0053) but the majority of fracture prevention benefit occurred after a DFS event (HR 0.3; 95%CI 0.17, 0.53; P