Practical update for the use of bone-targeted agents in patients with bone metastases from metastatic breast cancer or castration-resistant prostate cancer.

D Southcott,A Awan,M Clemons,R Fernandes,K Ghate

doi:10.3747/co.27.6631

Abstract

Bone metastases are a significant source of morbidity and mortality for patients with breast and prostate cancer. In this review, we discuss key practical themes regarding the use of bone-targeted agents (btas) such as bisphosphonates and denosumab for managing bony metastatic disease. The btas both delay the onset and reduce the incidence of skeletal-related events (sres), defined as any or all of a need for radiation therapy or surgery to bone, pathologic fracture, spinal cord compression, or hypercalcemia of malignancy. They have more modest benefits for pain and other quality-of-life measures. Regardless of the benefits of btas, it should always be remembered that the palliative management of metastatic bone disease is multimodal and multidisciplinary. The collaboration of all disciplines is essential for optimal patient care. Special consideration is given to these key questions: ■ What are btas, and what is their efficacy?■ What are their common toxicities?■ When should they be initiated?■ How do we choose the appropriate bta?■ What is the appropriate dose, schedule, and duration of btas?

Highlights

Bone is the most common site of metastasis in many malignancies, including breast (70%), prostate (70%–90%), thyroid (60%), lung (35%), and renal cell carcinomas (35%), and bone metastases can be associated with morbidity and mortality[1,2]
The efficacy of bone-targeted agents is commonly assessed using the rate of skeletal-related events, which occur in approximately 27% –40% of patients with metastatic castration-resistant prostate cancer and metastatic breast cancer[2,8]
For the purposes of this review, we focus on the two types of btas that are approved for use in clinical practice: bisphosphonates and denosumab

Summary

INTRODUCTION

Bone is the most common site of metastasis in many malignancies, including breast (70%), prostate (70%–90%), thyroid (60%), lung (35%), and renal cell carcinomas (35%), and bone metastases can be associated with morbidity and mortality[1,2]. The joint 2017 guideline from the American Society of Clinical Oncology and Ontario Health (Cancer Care Ontario) for mbca recommends the use of zoledronate at a dose of 4 mg given intravenously over no less than 15 minutes[18]. A more recent trial evaluating the noninferiority of 12-weekly compared with 4-weekly dosing for btas in patients with breast cancer and crpc showed that a dose–de-escalated schedule can be applied to pamidronate[44]. One study investigating the benefit of switching from pamidronate to zoledronic acid in patients with high-risk disease did not show any reduction in sres or qol and pain scores, and switching between bisphosphonates is not recommended[47].

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SUMMARY

Findings

Key Points