Efficacy of zoledronic acid in postmenopausal Japanese women with early breast cancer receiving adjuvant letrozole: 36-month results.

Abstract

e20510 Background: We reported 12-month results of upfront zoledronic acid (ZOL) therapy, which prevented bone loss in postmenopausal Japanese women who were receiving adjuvant letrozole, confirming the Z-FAST and ZO-FAST studies results. But the examination in the long term of aromatase inhibitor-associated bone loss has not been proved in the Japanese or Asia women. Methods: Postmenopausal women with hormone receptor positive early breast cancer (BC) patients receiving adjuvant letrozole were randomly assigned to receive either upfront or delayed-start ZOL (4mg intravenously every 6 months) for 5 years. The delayed group received ZOL when lumbar spine (L2-L4) BMD decreased to less than young adult mean (YAM) – 2.0 S.D or when a nontraumatic fractured occurred. The primary endpoint of this study was to compare the changes in L1-L4 BMD at month 12 between the groups. Secondary endpoints, measured at other predetermined timepoints, included comparing changes in L1-L4, L2-L4and total hip (TH) BMD and markers of bone turnover, fracture incidence, and time to disease recurrence. We report the results of 36-month interim analysis. Results: At 36 months, mean change in L1-L4 BMD was 10.7% higher in the upfront group than in the delayed group ( 95% CI, 9.2% to 12.1%; p< 0.001 ), L2-L4BMD was 10.9% higher ( 95% CI, 9.3% to 12.5%; p< 0.001 ), and TH BMD was 6.7% higher ( 95% CI, 5.3% to 8.1%; p< 0.001 ). The incidence of fracture was not significantly different between each group (upfront, 1(1.0%) vs. delayed, 4(4.1%)). Disease recurrence was reported in 3 upfront (3.1%) and 1 delayed (1.0%) patients. By month 36, 11 patients (11.3%) in the delayed group initiated ZOL therapy. There was no significant difference of adverse events other than fever with ZOL at the first treatment between the two groups. Conclusions: Upfront ZOL seems to be the preferred treatment strategy versus delayed administration, as it significantly and progressively increases BMD in postmenopausal Japanese women with early BC who were receiving adjuvant letrozole for 36 months. Clinical trial information: UMIN000001104.