Efficacy of zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: 36-month results of the ZO-FAST Study.
BACKGROUND
Aromatase inhibitors (AIs) are accepted as adjuvant therapy for postmenopausal women (PMW) with hormone-responsive early breast cancer (EBC) with superior efficacy to tamoxifen. However, increased bone loss is associated with AIs.


METHODS
PMW with EBC receiving letrozole (2.5 mg/day for 5 years) were randomly assigned to immediate zoledronic acid (ZOL; 4 mg every 6 months) or delayed ZOL (initiated only for fracture or high risk thereof).


RESULTS
Patients (N = 1065) had a median age of 58 years; 54% had received prior adjuvant chemotherapy. At 36 months, mean change in L2-L4 bone mineral density (BMD) was +4.39% for immediate versus -4.9% for delayed ZOL (P < 0.0001). Between-group differences were 5.27% at 12 months, 7.94% at 24 months, and 9.29% at 36 months (P < 0.0001 for all). At 36 months, the immediate-ZOL group had a significant 41% relative risk reduction for disease-free survival (DFS) events (P = 0.0314). Adverse events are consistent with the known safety profiles of the study drugs.


CONCLUSIONS
At 36 months, immediate ZOL was more effective in preserving BMD during letrozole therapy. Immediate versus delayed ZOL led to significantly improved DFS. Benefits are observed in the context of a favorable, well-established safety profile for letrozole and ZOL.
Eidtmann
H
H
Klinik für Gynäkologie und Geburtshilfe, Universitäts Frauenklinik Kiel, Germany. Electronic address: eidtmann@email.uni-kiel.de.
de Boer
R
R
Medical Oncology, Royal Melbourne Hospital, Victoria, Australia.
Bundred
N
N
South Manchester University Hospital, Academic Surgery, Education and Research Center, Manchester, UK.
Llombart-Cussac
A
A
Hospital Universitàri Arnau de Vilanova, Lleida, Spain.
Davidson
N
N
Broomfield Hospital, Chelmsford, Essex, UK.
Neven
P
P
Hospital Gasthuisberg, Leuven, Belgium.
von Minckwitz
G
G
German Breast Group, Frankfurt, Germany.
Miller
J
J
Novartis Pharmaceuticals Corporation, Florham Park, NJ, USA.
Schenk
N
N
Novartis Pharmaceuticals Corporation, Florham Park, NJ, USA.
Coleman
R
R
Academic Unit of Clinical Oncology, Weston Park Hospital, Sheffield, UK.
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001862:Bone Resorption / Q000139:chemically induced / Q000188:drug therapy; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D004164:Diphosphonates / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D000077289:Letrozole; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D009570:Nitriles / Q000627:therapeutic use*; D017698:Postmenopause; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D009570:Nitriles; D014230:Triazoles; D000077211:Zoledronic Acid; D000077289:Letrozole