(ChemotherapyAdvisor) – Initiating zoledronic acid (zoledronate) therapy immediately, rather than waiting for bone mineral density (BMD) declines or fractures to occur, improves bone health and disease-free survival (DFS) among postmenopausal women with early hormone-responsive breast cancer who are taking letrozole, according to a study published in the Annals of Oncology.
“Immediate zoledronate in postmenopausal women receiving letrozole preserved BMD and is associated with improved DFS (disease-free survival) compared with letrozole alone,” reported an international team of researchers and lead author Rob E. Coleman, MD, FRCP, professor and the Academic Unit of Clinical Oncology at the Sheffield Cancer Research Centre, at the University of Sheffield in England.
Aromatase inhibitors are “generally more effective than tamoxifen” as adjuvant endocrine therapy agents among postmenopausal women with hormone-responsive early-stage breast cancer – but these agents are associated with bone loss and increased risk of fractures, the authors noted.
In the ZO-FAST trial, postmenopausal women receiving adjuvant therapy with the oral non-steroidal aromatse inhibitor letrozole (2.5mg/day for 5 years; N=1,065) for early-stage breast cancer were randomly assigned to receive immediate zoledronate (4mg every 6 months for 5 years) or delayed zoledronate (initiated after fracture or BMD decline).
Final 60-month results from the trial show that the immediate zoledronate-arm patients enjoyed superior BMDs (+4.3% vs -5.4% among the delayed zoledronate-arm patients; P<0.0001), the authors reported.
Immediate administration of zoledronate also “substantially improved DFS,” they wrote (HR, 0.62; 95% CI: 0.41-0.93; P=0.0239).
Overall survival (OS) did not differ between the immediate- and delayed-zoledronic administration groups, however (P=0.146).
Patients receiving immediate zoledronate also experienced a 34% reduction in the risk of DFS events (disease recurrence or death; HR, 0.66; P=0.0375), “with fewer local (0.9% versus 2.3%) and distant (5.5% versus 7.7%) recurrences versus delayed zoledronate,” the authors reported.
Receiving zoledronate later was still better than not receiving zoledronate at all, the authors added.
“In the delayed group, delayed initiation of zoledronate substantially improved DFS versus no zoledronate (HR, 0.46; P=0.0334),” they wrote.
Osteonecrosis of the jaw was confirmed in 3 patients. Atrial fibrillation, renal adverse events and fractures were “statistically similar” in immediate- and delayed-zoledronate arms; no effects on patients’ cholesterol levels were found.