The American Society of Clinical Oncology (ASCO) updated its recommendation last month on the role of bone-modifying agents in the prevention of skeletal-related events (SREs) for metastatic breast cancer patients with bone metastases (DOI: 10.1200/JCO.2010.32.520). The new recommendations include a novel treatment option and recommendations regarding a potential rare but serious side effect, osteonecrosis of the jaw.
After searching all relevant literature published between 2003 and 2010 that had SREs or time to SREs as the primary outcome, ASCO now recommends bone-modifying agent therapy for breast cancer patients with evidence of bone metastases. The bone metastases diagnosis must be confirmed by X-ray, CT or MRI, and not just an abnormal bone scan in order for a patient to qualify for treatment.
The recommendations include either denosumab (Prolia from Amgen), or pamidronate(Drug information on pamidronate) (Novartis’s Aredia) and zoledronic acid (Novartis’s Zometa). Denosumab is a monoclonal antibody that works against the receptor activator of nuclear factor-kappa beta ligand (RANKL); it was approved in 2010. The two Novartis drugs are both IV-administed bisphosphonates. According to the panel that wrote the updated guidelines, "There is insufficient evidence to demonstrate greater efficacy of one bone-modifying agent over another."
The recommendations include a dental examination and appropriate preventive dentistry before taking any bone-modifying agents because of the small percentage of cases of osteonecrosis of the jaw that have been observed in clinical trials. Although most osteonecrosis of the jaw cases have occurred in patients taking IV bisphosphonates and bone-modifying agents who underwent invasive dental procedure, there have been spontaneous cases reported, including in patients taking oral biosphosphonates.
Because of significant data on the effects of bisphosphonates on kidney function, the panel reviewed whether there are renal safety concerns with bone modifying agents. The guidelines suggest that patients with > 60mg/ml creatinine clearance do not require any changes in bisphosphonate administratation, but serum creatinine levels should be monitored before each IV treatment dose. Additionally, patients taking denosumab with a creatinine clearance less than 30 ml/min or who are undergoing dialysis need to be monitored for hypocalcemia, according to the guidelines.
The optimal duration of bone-modifying agent therapy has not been updated and remains the same as the 2003 guidelines. Likewise, the guidelines still suggest that biochemical markers should not be used to monitor the effectiveness of the bone-modifying agent treatment except in clinical trials, as there have not been any new studies that suggest biomarkers have any clinical utility.