ASCO/CCO Focused Guideline Update on Role of Bone-Modifying Agents in Metastatic Breast Cancer

By Matthew Stenger
February 10, 2018

AS REPORTED BY Catherine Van Poznak, MD, FASCO, of the University of Michigan, Ann Arbor, and colleagues in the Journal of Clinical Oncology, ASCO and Cancer Care Ontario (CCO) have collaborated in providing a focused update for the ASCO clinical practice guideline on the role of bone-modifying agents in metastatic breast cancer.¹ A joint update committee conducted a targeted systematic literature review to identify relevant studies; the update was informed by data from three phase III noninferiority trials of dosing intervals, one systematic review and meta-analysis of studies of de-escalation of bone-modifying agents, and two randomized trials of bone-modifying agents in control of pain secondary to bone metastases. The update committee was co-chaired by Dr. Van Poznak and Beverly Moy, MD, FASCO, of Massachusetts General Hospital.

 Updated recommendations and recommendations unchanged from the 2011 guideline are reproduced/summarized here. For updated recommendations, the type of recommendation, evidence quality, and strength of recommendation are shown in brackets. 

Key Recommendations 

PATIENTS WITH BREAST CANCER who have evidence of bone metastases should be treated with bone-modifying agents. Options include denosumab (Xgeva) at 120 mg subcutaneously every 4 weeks; pamidronate at 90 mg intravenously (IV) every 3 to 4 weeks; or zoledronate at 4 mg IV every 12 weeks or every 3 to 4 weeks. 

2017 Guideline Updates 

• As recommended in the 2011 version of the ASCO bone-modifying agents guideline, patients with breast cancer who have evidence of bone metastases should be treated with bone-modifying agents. One bone-modifying agent is not recommended over another. If patients are treated with zoledronate at 4 mg IV administered over no less than 15 minutes, dosing options are every 12 weeks or every 3 to 4 weeks. [Type = evidence based, benefits outweigh harms; evidence quality = high; strength of recommendation = strong]

Recommendation Updated for 2017 Guideline 

• The analgesic effects of bone-modifying agents (denosumab, pamidronate, or zoledronate) are modest, and they should not be used alone for bone pain. The panel recommends the current standard of care for supportive care and pain management be applied. This can include analgesia, adjunct therapies, radiotherapy, surgery, systemic anticancer therapy, and referral to supportive care and pain management. Evidence of a clinically meaningful benefit is insufficient to support the use of one bone-modifying agent over another. Further research is needed on this clinical question. [Type = evidence based, benefits outweigh harms; evidence quality = low; strength of recommendation = weak] 

Recommendations Unchanged From 2011 Guideline Update 

• Bone-modifying agents are recommended for patients with metastatic breast cancer with evidence of bone destruction. One bone-modifying agent is not recommended over another. 
• The mechanism of action, as well as the potential benefits and harms, should be taken into account when considering the long-term use of bone-modifying agents.
• In patients with creatinine clearance > 60 mL/min, no change in dosage, infusion time, or interval is required; creatinine level should be monitored with each IV bisphosphonate dose.
• In patients with creatinine clearance < 30 mL/min or who are on dialysis who may be treated with denosumab, close monitoring for hypocalcemia is recommended.
• All patients should have a dental examination and preventive dentistry before using a bone-modifying agent.
• Use of biochemical markers to monitor use of a bone-modifying agent is not recommended for routine care. 

Additional information is available at www.asco.org/breast-cancer-guidelines and www.asco.org/guidelineswiki. ■

DISCLOSURE: For full disclosures of the study authors, visit www.jco.ascopubs.org. 

REFERENCE 

1. Van Poznak C, Somerfield MR, Barlow WE, et al: Role of bone-modifying agents in metastatic breast cancer: An American Society of Clinical Oncology–Cancer Care Ontario focused guideline update. J Clin Oncol 35:3978- 3986, 2017.

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