Integrated analysis of zoledronic acid for prevention of aromatase inhibitor-associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole.
BACKGROUND
The interim (12-month) results of two similarly designed, ongoing studies (the Zometa-Femara Adjuvant Synergy Trials [Z-FAST and ZO-FAST]) suggest that zoledronic acid (4 mg intravenously every 6 months) when initiated with adjuvant letrozole increases bone mineral density (BMD) of the lumbar spine (LS) in postmenopausal women with early-stage breast cancer compared with patients who receive zoledronic acid only when bone loss became clinically significant or a fragility fracture occurred.


METHODS
An integrated analysis was performed to maximize the value of the large pool of data from the two studies in answering clinically relevant questions. The primary objective was to compare the change in LS BMD at month 12. Secondary objectives included comparing (a) the change in total hip (TH) BMD, (b) changes in bone turnover marker concentrations, (c) time to disease recurrence, and (d) safety at month 12.


RESULTS
The integrated analysis included 1,667 patients. At month 12, LS BMD was 5.2% higher in the upfront group than in the delayed group; TH BMD was 3.5% higher. N-telopeptide and bone-specific alkaline phosphatase concentrations decreased by 21.3% and 12.8% in the upfront group and increased by 21.7% and 24.9% in the delayed group, respectively (p < .0001 for intergroup comparisons). Fewer patients receiving upfront zoledronic acid experienced disease recurrence than patients in the delayed group-seven patients (0.84%) versus 17 patients (1.9%) (p = .0401). Fracture rates were similar. No confirmed osteonecrosis of the jaw was reported.


CONCLUSIONS
The results of this analysis strengthen the statistical validity of the preliminary results of the Z-FAST and ZO-FAST studies, showing that upfront zoledronic acid prevents aromatase inhibitor-associated bone loss more effectively than delayed-start zoledronic acid in postmenopausal women with early-stage breast cancer receiving letrozole. Additionally, disease recurrence appears to be lower with upfront zoledronic acid, but further follow-up is needed to confirm these interim results.
Brufsky
Adam
A
Magee-Womens Hospital, Pittsburgh, Pennsylvania 15123, USA. brufskyam@upmc.edu
Bundred
Nigel
N
Coleman
Robert
R
Lambert-Falls
Rosemary
R
Mena
Raul
R
Hadji
Peyman
P
Jin
Lixian
L
Schenk
Nora
N
Ericson
Solveig
S
Perez
Edith A
EA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D047072:Aromatase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000077289:Letrozole; D008159:Lumbar Vertebrae / Q000473:pathology; D008875:Middle Aged; D009570:Nitriles / Q000494:pharmacology / Q000627:therapeutic use*; D015663:Osteoporosis, Postmenopausal / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use*; D000077211:Zoledronic Acid
D047072:Aromatase Inhibitors; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D009570:Nitriles; D014230:Triazoles; D000077211:Zoledronic Acid; D000077289:Letrozole