Bone-Modifying Therapy for Metastatic Breast Cancer

The use of bone-modifying therapy to reduce skeletal morbidity in patients with bone metastases should be considered.[151] Results of randomized trials of pamidronate and clodronate in patients with bony metastatic disease show decreased skeletal morbidity.[152-154][Level of evidence A3] Zoledronate has been at least as effective as pamidronate.[155]

The optimal dosing schedule for zoledronate was studied in CALGB-70604 (Alliance; NCT00869206), which randomly assigned 1,822 patients, 855 of whom had metastatic breast cancer, to receive zoledronic acid every 4 weeks or every 12 weeks.[156] Skeletal-related events were similar in both groups, with 260 patients (29.5%) in the zoledronate every-4-week dosing group and 253 patients (28.6%) in the zoledronate every-12-week dosing group experiencing at least one skeletal-related event (risk difference of -0.3% [1-sided 95% CI, -4% to infinity]; P < .001 for noninferiority).[156][Level of evidence B1] This study suggests that the longer dosing interval of zoledronate every 12 weeks is a reasonable treatment option.

The monoclonal antibody denosumab inhibits the receptor activator of nuclear factor kappa beta ligand (RANKL). A meta-analysis of three phase III trials (NCT00321464, NCT00321620, and NCT00330759) comparing zoledronate versus denosumab for management of bone metastases suggests that denosumab is similar to zoledronate in reducing the risk of a first skeletal-related event.[157]

For more information about bisphosphonates, see Cancer Pain.