Zoledronic acid (zoledronate) for postmenopausal women with early breast cancer receiving adjuvant letrozole (ZO-FAST study): final 60-month results

Abstract

Immediate zoledronate in postmenopausal women receiving letrozole preserved BMD and is associated with improved DFS compared with letrozole alone. Clinical Trials Registration No NCT00171340.

Mechanisms of action of bisphosphonates in oncology: a scientific concept evolving from antiresorptive to anticancer activities

“…17 Similarly, in the ZO-FAST trial, fewer recurrences were reported in the immediate-zoledronate group compared with the delayed-zoledronate group (5 vs 12 at 60 months' follow-up). 19 Although not statistically significant, locoregional recurrences in the Z-FAST trial also occurred in slightly more patients in the delayed-zoledronate group compared with the immediatezoledronate group (4 vs 2 at 61 months' follow-up). 20 Thus, zoledronate released from bone might therefore block tumor self-seeding.…”

“…7 Designed primarily to investigate the bone-preserving activity of zoledronate during adjuvant therapy with aromatase inhibitors, the european Zometa-Femara Adjuvant Synergy Trial ZO-FAST (n ¼ 1065) showed after 60 month's follow-up that the immediate addition of zoledronate to adjuvant letrozole therapy reduced the risk of disease progression by 34% in postmenopausal women with endocrine-responsive, stage I-III breast cancer, when compared with patients in the 'delayed' group who received zoledronate only if bone mineral density declined or non-traumatic fracture occurred ( Table 1). 19 In the companion North American trial to ZO-FAST (the ZometaFemara Adjuvant Synergy Z-FAST study; n ¼ 602), immediate zoledronate also reduced disease recurrence, but did not result in a statistically significant difference in disease-free survival compared with the delayed-zoledronate group (16 vs 21 at 61 months' follow-up) ( Table 1). 20 However, taken together these findings [17][18][19][20] suggested that zoledronate may improve diseasefree survival in breast cancer patients.…”

“…19 In the companion North American trial to ZO-FAST (the ZometaFemara Adjuvant Synergy Z-FAST study; n ¼ 602), immediate zoledronate also reduced disease recurrence, but did not result in a statistically significant difference in disease-free survival compared with the delayed-zoledronate group (16 vs 21 at 61 months' follow-up) ( Table 1). 20 However, taken together these findings [17][18][19][20] suggested that zoledronate may improve diseasefree survival in breast cancer patients.…”

Guidelines for the diagnosis, prevention and management of osteoporosis

“…Over time, an increasingly conservative threshold has been considered, up to nearnormal, especially in the presence of other independent risk factors (58,59). However, based on the following factors: i) the lack of evidence for a validated Tscore threshold (only based on expert opinion) and the uncertainty on the predictive value of BMD for fracture risk in this patient population; ii) a particularly fast rate of bone loss in all forms of osteoporosis induced by adjuvant hormonal therapy, as an independent risk factor; iii) a very high prevalence of osteoporosis/fractures and/or other risk factors for fracture in patients with breast or prostate cancer; iv) the strong evidence that treatment with antiresorptives is more effective when used before than after a fracture or BMD loss has occurred, in both men and women (either pre-or post-menopausal) (60,63); v) the evidence that fracture risk reduction (with denosumab) is independent of BMD values at initiation of antiresorptive therapy (61).…”

Bone remodeling markers and bone metastases: From cancer research to clinical implications

“…On the basis of the hypothesis that an increased bone metabolism may facilitate the development of BM, prior studies tested the added benefit of ZA in the adjuvant treatment of early breast cancer. A benefit in terms of relapse-free survival was found in premenopausal women under complete estrogen blockage (goserelin with either tamoxifen or anastrazol; ABCSG-12; Gnant et al 56 ), in postmenopausal women under aromatase inhibitors (letrozol; ZO-FAST; Coleman et al 57 ) and in women under systemic adjuvant therapy who had undergone menopause more than 5 years earlier (AZURE; Coleman et al 58 ). Moreover, an individual patient data meta-analysis condensing information from 41 randomized trials that compared bisphosphonates (BPs) with placebo or no BPs in patients with breast cancer (n ¼ 17 016, of which 10 540 were postmenopausal women) further demonstrated a 34% improvement in the rate of bone recurrences (Po0.001) and a novel 17% improvement in the rate of breast cancer death (P ¼ 0.004) in postmenopausal women treated with BPs.…”