Zoledronic acid effectively prevents aromatase inhibitor-associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole: Z-FAST study 36-month follow-up results.
BACKGROUND
Postmenopausal women with breast cancer receiving adjuvant aromatase inhibitors (AIs) are at risk for accelerated bone loss and subsequent fractures. The ongoing Zometa-Femara Adjuvant Synergy Trial (Z-FAST) is evaluating the efficacy and safety of zoledronic acid in preventing such bone loss.


METHODS
In this multicenter study, postmenopausal women with early hormone receptor-positive breast cancer receiving adjuvant letrozole were randomized to receive up-front or delayed-start zoledronic acid (ZA; 4 mg intravenously every 6 months) for 5 years. Delayed-start ZA was administered if the lumbar spine (LS) or total hip (TH) T score fell below -2.0 or a nontraumatic fracture occurred. The primary endpoint was to compare the change from baseline in LS bone mineral density (BMD) between groups at month 12; secondary endpoints, measured at other predetermined timepoints, included comparing changes in TH BMD, LS BMD, and markers of bone turnover, fracture incidence, and time to disease recurrence. Herein, we report the results of the 36-month interim analysis.


RESULTS
Overall, 301 patients were randomized to each group. At month 36, the absolute difference in mean LS and TH BMDs between the up-front and delayed groups was 6.7% and 5.2%, respectively (P < .0001 for both). Although this study was not designed to show antifracture efficacy, the incidence of fractures was slightly higher in the delayed group (up-front, 17 [5.7%] vs. delayed, 19 [6.3%]) but not statistically significant (P = .8638). Pyrexia (27 [9%] vs. 6 [2%]; P = .0002) and bone pain (39 [13%] vs. 20 [6.7%]; P = .01) were more common in up-front patients; cough (13 [4.3%] vs. 27 [9%]; P = .03) was more common in delayed patients. No severe renal dysfunction or confirmed cases of osteonecrosis of the jaw were reported. Disease recurrence was reported in 9 up-front (3.0%) and 16 delayed (5.3%) patients (Kaplan-Meier analysis, P = .127), with an absolute decrease of 2.3%.


CONCLUSIONS
Up-front ZA more effectively prevents AI-associated bone loss in postmenopausal women with early breast cancer than delaying therapy until substantial bone loss or fracture occurs.
Magee-Womens Hospital, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15123, USA. brufskyam@upmc.edu
Adam M
AM
Brufsky
Linda D
LD
Bosserman
Richard R
RR
Caradonna
Barbara B
BB
Haley
C Michael
CM
Jones
Halle C F
HC
Moore
Lixian
L
Jin
Ghulam M
GM
Warsi
Solveig G
SG
Ericson
Edith A
EA
Perez
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D047072:Aromatase Inhibitors / Q000009:adverse effects*; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D000077289:Letrozole; D008875:Middle Aged; D009367:Neoplasm Staging; D009570:Nitriles / Q000009:adverse effects*; D015663:Osteoporosis, Postmenopausal / Q000139:chemically induced / Q000188:drug therapy*; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects*; D000077211:Zoledronic Acid
D047072:Aromatase Inhibitors; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D009570:Nitriles; D014230:Triazoles; D000077211:Zoledronic Acid; D000077289:Letrozole