A phase III, multicenter, randomized, controlled study of maximum androgen blockade with versus without zoledronic acid in treatment-naïve prostate cancer patients with bone metastases: Results of ZAPCA study.

Abstract

150 Background: Zoledronic acid (ZA) is proved to be useful for the prevention of skeletal-related events (SREs) in men with castration-resistant prostate cancer and bone metastases, but its early use combined with androgen deprivation therapy (ADT) in men with hormonal treatment-naïve prostate cancer and bone metastases is controversial. Methods: A total of 227 men with hormonal treatment-naïve prostate cancer and bone metastases were randomly assigned in a 1:1 ratio to receive zoledronic acid (4mg intravenously every 4 weeks up to 2 years) along with ADT (LH-RH analogue + bicalutamide, MZ group) or ADT alone (MAB group). Stratification factors were PSA (<200ng/ml vs. ≥200ng/ml), EOD (extent of diseases) grade (1,2 vs. 3,4) and Gleason score (<7 vs. ≥8). The primary end point was time to treatment failure (TTTF), defined as 3 consecutive rise of PSA from the nadir, clinical progression, SRE, death or cessation of protocol therapy for any reason. Results: The median follow-up was 41.1 months. The median TTTF was 12.4 months in MZ group (95% CI, 10.6 to 16.6) and 9.7 months in MAB group (95% CI, 8.9 to 12.6; hazard ratio, 0.754; 95% CI, 0.567 to 1.003; log-rank P= .051). In a subset of men with baseline PSA levels <200ng/mL, the median TTTF was 23.7 months in MZ group (95% CI, 15.2 to 31.3) and 9.8 months in MAB group (95% CI, 6.6 to 17.0; hazard ratio, 0.575; 95% CI, 0.354 to 0.933; log-rank P= .023). An exploratory multivariate analysis using Cox proportional hazards model identified MZ group, age less than 80, and EOD ≤2 as independent factors associated with better TTTF. Conclusions: In men with hormonal treatment naïve prostate cancer with bone metastases, concurrent use of ZA with ADT did not show a significant advantage over ADT alone regarding TTTF. However, in a subgroup of men with lower baseline PSA levels, ZA significantly prolonged TTTF, compared with ADT alone. Clinical trial information: NCT00685646.