Randomized Trial of Adjuvant Zoledronic Acid in Postmenopausal Women With High-Risk Breast Cancer

Abstract

Purpose We present the results of a randomized, multicenter clinical trial of adjuvant ZA in postmenopausal women with high-risk breast cancer. The primary objective was change in bone mineral density (BMD) at the lumbar spine and femoral neck at 1 year. Secondary objectives included change in calcaneal BMD, disease-free survival (DFS), overall survival (OS), and toxicity. Patients and Methods Postmenopausal women with stage II/III breast cancer diagnosed up to five years prior were eligible and randomized to either observation or ZA 4 mg IV every 3 months. BMD testing was performed at 0, 6 and 12 months. Results Sixty-eight women were enrolled: 36 (ZA) and 32 women (observation). The population was a median of 2 years from diagnosis and the majority received tamoxifen during study. There was a significant difference in the mean change from baseline to 1 year follow-up for lumbar spine (increased by 4.28±0.62%; p=0.01), total femur (increased by 1.9±0.4%; p=0.03), trochanter (increased by 2.97±0.69%; p=0.03) and calcaneal BMD (increased by 2±0.57%; p=0.01) in favor of the ZA arm. No significant difference in the mean change for the femoral neck was seen. No significant differences in DFS or OS were observed. Conclusion ZA significantly improved the BMD at multiple skeletal sites in postmenopausal women largely on tamoxifen. No new safety signals were noted. There were insufficient events to comment on DFS or OS.

Adjuvant Bisphosphonates in Patients with Breast Cancer: Does the Potency Matter?

“…In eight trials (10,927 patients) an N-BP was tested (zoledronic acid, pamidronate, ibandronate or risedronate) [12][13][14][15][16][17][18][19]. In the clodronate trial subset, patients treated with antiresorptive therapy had a nonsignificant reduction in the risk of death compared with those in the control arms (HR of death: 0.86; 95% CI: 0.67-1.11), with a strong heterogeneity (I 2 = 61%) driven by a single trial [8].…”

“…To provide information on the effect of adjuvant N-BPs compared with clodronate on survival in early breast cancer, we performed a literaturebased meta-analysis of 12 randomized prospective trials comparing different BPs with either placebo or no antiresorptive therapy [8][9][10][11][12][13][14][15][16][17][18][19]. For all of these studies, data on OS were reported in the most updated publication.…”

Bisphosphonates in the Adjuvant Setting of Breast Cancer Therapy—Effect on Survival: A Systematic Review and Meta-Analysis

“…We appraised the rate of patients lost to follow up and in the majority of the studies the rate was <10%. In three trials the rate was higher (Range – 17–42%; [19]–[20], [28]). …”

“…Ten trials (13,571 patients) were eligible for the meta-analysis of overall survival [13]–[17], [19], [22], [24], [28]–[29]. The numbers of randomly assigned and analyzed patients in each included trial are described in Table 1.…”

Cost–Utility of Adjuvant Zoledronic Acid in Patients with Breast Cancer and Low Estrogen Levels

“…Many of the completed trials investigated adjuvant bisphosphonate therapy for its effect on bone health [7][8][9][10][11][12] . Those trials often compared early with delayed bisphosphonate therapy rather than adjuvant za with no bisphosphonate, or considered primary endpoints that were unrelated to breast cancer outcomes.…”