Denosumab Compared With Zoledronic Acid for the Treatment of Bone Metastases in Patients With Advanced Breast Cancer: A Randomized, Double-Blind Study

Abstract

Denosumab was superior to zoledronic acid in delaying or preventing SREs in patients with breast cancer metastatic to bone and was generally well tolerated. With the convenience of a subcutaneous injection and no requirement for renal monitoring, denosumab represents a potential treatment option for patients with bone metastases.

Osteonecrosis of the jaws in patients assuming oral bisphosphonates for osteoporosis: A retrospective multi-hospital-based study of 87 Italian cases

“…One limitation of our research was the non-controlled study design which may have led to an overestimation of BRONJ in non cancer-patients. There are very few RCTs dealing with this issue [1,8,18,19,28,39,51].…”

Medical Treatment of Breast Cancer Bone Metastasis: From Bisphosphonates to Targeted Drugs

“…Denosumab is mostly cleared through the reticuloendothelial system. Although renal associated adverse effects are nearly equal between zoledronic acid and denosumab, severe renal associated adverse events (1.5% vs 0.2%) and renal failure (1.5% vs 0.2%) are more frequent with zoledronic acid (Stopeck et al, 2010). In a meta-analysis risk of renal adverse events was found significantly high with zoledronic acid in patients with breast cancer, prostate cancer and other solid tumors (RR 0.76; 95%CI, 0.59-0.98) (Sun et al, 2013).…”

“…In patients treated with denosumab, ONJ incidence is similar to zoledronic acid (2%-1.4% respectively p=0.39) (Stopeck et al, 2010). Longer duration of therapy, higher cumulative doses, treatment with more potent bisphosphonates (zoledronic acid and pamidronate), history of recent alveolar trauma and inflammatory dental disease are known risk factors for ONJ (Hoff et al, 2008;Hoff et al, 2011).…”

“…Four weekly 120mg administration of denosumab was the most effective one in suppressing the bone turnover with similar adverse events (Lipton et al, 2007). The largest clinical trial (2046 patients with breast cancer bone metastasis) that compared denosumab with zoledronic acid has been published in 2010 (Stopeck et al, 2010). Denosumab was superior to zoledronic acid in delaying time to first on-study SRE (HR, 0.82; 95%CI, 0.71 to 0.95; p<0.001 noninferiority; p=0.01 superiority) and in reducing risk of multiple SRE (p=0.001).…”

“…Hypocalcemia and hypophosphatemia are more common with denosumab (Stopeck et al, 2010;Lipton et al, 2012). If no contraindication is present, to prevent hypcalcemia calcium and vitamin D supplementation is recommended to all patients receiving bone modifying agent with breast cancer bone metastasis.…”