[107] An integrated analysis of zoledronic acid (ZA) for prevention of aromatase inhibitor associated bone loss (AIBL) in postmenopausal women (PMW) with early breast cancer (BCa) receiving adjuvant letrozole (LET).

Brufsky A, Bundred N, Coleman R, Lambert-Falls R, Mena R, Dong M, Schenk N, Lacerna L, Perez E.. Novartis Pharmaceuticals Corporation, East Hanover, NJ

Background: In PMW with BCa, treatment with aromatase inhibitors (AIs) results in nearly complete ablation of estrogen production, leading to accelerated bone loss. With the increased use of AIs as adjuvant therapy for early BCa, there is an urgent clinical need to investigate the prevention of AIBL. The use of ZA in preventing AIBL was studied in North America with the Z-FAST trial, and the rest of world with the parallel-designed trial ZO-FAST. The combined power of these trials was investigated through an integrated analysis of the 12 mos data.
Methods: Data were collected from the Z-FAST and ZO-FAST trials involving a total of 1,667 women. PMW with stage I-IIIa ER+ and/or PR+ BCa starting LET (2.5mg qd x 5 yrs) were randomized to upfront ZA (4 mg 15 min IV infusion q 6 mos) vs delayed ZA. The delayed group will receive ZA treatment when either post-baseline T-score decreases <-2 or in case of a non-traumatic fracture. The main focus of this analysis is on the percent change in lumbar spine (LS) BMD at 12 mos.
Results: Baseline characteristics were similar between groups. The median duration of LET use is 13.4 months in the upfront group and 12.9 months in the delayed group. At 12 mos, the mean percentage change in LS BMD from baseline was 2.0% in the upfront group (n=715) and -3.1% in the delayed group (n=719), resulting in a significant difference of 5.1% between groups (p<0.001). The mean percentage change in total hip (TH) BMD was 1.2% in the upfront group (n=713) and -2.2% in the delayed group (n=723), resulting in a significant difference of 3.4% between groups (p<0.001). At 12 mos, 11% of patients in the delayed group started ZA due to post-baseline T-score decrease below -2.0 or the occurrence of a clinical fracture. The bone marker substudy (n=633) showed persistent suppression of both serum N-telopeptide and bone-specific alkaline phosphatase over 12 months in favor of the upfront group. 2.2% patients in the upfront group and 2.1% patients in the delayed group had fractures. 0.8% patients in the upfront group and 2.2% patients in the delayed group experienced progression of breast cancer. Both LET and ZA were safe and well tolerated. No serious renal adverse events or cases of osteonecrosis of the jaw (ONJ) were reported.
Discussion: The results of this integrated analysis provide further confirmation that ZA at a dose of 4mg IV q 6 mos is effective for the prevention of bone loss associated with adjuvant aromatase inhibitor therapy in PMW with early BCa. The optimal timing of initiation of ZA for the prevention of bone loss in patients with early breast cancer receiving adjuvant AI therapy requires further study. Additional integrated data, at 36 and 60 months follow-up, will be reported as it becomes available.

Thursday, December 14, 2006 5:00 PM

Poster Discussion Session I: Aromatase Inhibitors (5:00 PM-7:00 PM)