The American Society of Clinical Oncology has revised its guidelines on care of bone metastases in metastatic breast cancer to reflect expanded treatment options as well as concern about osteonecrosis of the jaw, a rare but serious side effect.
The new guideline, released Feb. 22, on the role of "bone modifying agents" are the first to include denosumab (Xgeva), a monoclonal antibody approved in 2010 that targets the receptor activator of nuclear factor-kappa beta ligand (RANKL). They also address use of the bisphosphonates pamidronate (Aredia) and zoledronic acid (Zometa), two other agents previously available in the United States.
"There is insufficient evidence to demonstrate greater efficacy of one bone-modifying agent over another," according to the expert panel that updated the guidelines. It noted that two other bisphosphonates, ibandronate (Boniva) and clodronate, are not approved in the United States for patients with breast cancer that has metastasized to the bone, and therefore not addressed in the new guidelines.
The panel said it replaced the term bisphosphonates with "bone-modifying agents" in the name of the guidelines in order to be able to incorporate data on new types of agents, including osteoclast inhibitors, in future updates.
The "Updated Guideline on the Role of Bone-Modifying Agents in the Prevention and Treatment of Bone Metastases in Patients with Metastatic Breast Cancer" will be published soon in the Journal of Clinical Oncology, but is available for free online (pdf).
The recommendations include, also for the first time, advice regarding osteonecrosis of the jaw, a rare but potentially disastrous complication of therapy with bone-modifying agents that was recognized after publication of the 2003 guidelines (J. of Clin. Oncol. 2003;21:4042-4057). Before starting a bone-modifying agent, a patient should get a dental examination and receive preventive dentistry care, the panel recommends.
Bone-modifying agents should be used only in patients with breast cancer with evidence of bone metastases, the updated guideline states. Patients without bone metastases should not receive the drugs unless they are in a clinical trial. Diagnoses of bone metastases must by confirmed by X-ray, CT or MRI, and not rely on an abnormal bone scan to qualify for treatment.
Clinicians should start bone-modifying agents as soon as patients with metastatic breast cancer develop cancer bone pain, and should provide pain management.
There wasn’t enough evidence to recommend one agent over another. Two are given by IV and one subcutaneously. Recommended dosages are 120 mg subcutaneous denosumab every 4 weeks, or IV pamidronate 90 mg over no less than 2 hours every 3-4 weeks, or IV zoledronic acid 4 mg over no less than 15 minutes every 3-4 weeks, with no new data to support any changes from the last guideline.
Biochemical markers should not be used to monitor the effectiveness of bone-modifying agents except in clinical trials, the guideline states.
Data since 2003 on the effects of bisphosphonates on kidney function led to new recommendations on monitoring patients. No change in dosage, infusion time, or interval is needed for patients with creatinine clearance greater than 60 mL/minute. Clinicians should monitor the creatinine level with each IV bisphosphonate dose. When giving denosumab to patients with creatinine clearance less than 30 mL/minute or who are on dialysis, closely monitor for hypocalcemia, the guideline states.
Amgen, which markets denosumab, has provided payments for consulting, advising, or research to Dr. Catherine Van Poznak, co-chair of the guidelines panel, and to two other panelists. Dr. Van Poznak has received payments for consulting, advising, or research for Amgen, which markets denosumab and has received research funding from Novartis, which markets pamidronate and zoledronic acid. Dr. Von Roenn, co-chair of the guidelines panel, declared having no conflicts of interest. Two other panelists have been consultants, advisors, or recipients of honoraria from Roche or Abraxis BioScience.