De-Escalation of Bone-Targeted Agents Shows No Change in Efficacy, Safety


Researchers studied the quality of life, pain, Global Health Status, and adverse effects.

Investigators from Ottawa Hospital and the University of Ottawa have found that there is no significant difference in the efficacy or quality of life across dose levels for commonly used bone-targeted agents (BTA) such as denosumab and bisphosphonates for patients with bone metastases. The findings were presented at the 2019 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois.

The trial included 263 patients with bone metastases who had never received treatment for the condition or who were already receiving denosumab, pamidronate, or zoledronates. The patients were randomized to receive a chosen BTA previously listed every 12 or 4 weeks for 1 year. Investigators studied the quality of life, pain, Global Health Status, and adverse effects.

“The bone is the most common site of recurrence of breast and prostate cancer, and bone targeting agents reduce the incidence of skeletal events in such patients,” said Mark Clemons, MD, first author of the study, in an interview with Specialty Pharmacy Times®.

Of the 263 patients (approximately 60.8% breast cancer and 39.2% prostate cancer), 130 patients (49.4%) were randomized to 12-weekly and 133 patients (50.6%) to 4-weekly therapy of denosumab, zoledronate, and pamidronate. The data reported that there was no significant difference in reported rates of kidney failure (renal impairment), symptomatic hypocalcemia, osteonecrosis, or reduced blood flow of the jaw.

According to the American Cancer Society, bone metastasis is an area of bone that contains cancer that spread from elsewhere in the body; oftentimes, bone metastasis is located in the spine. Once cancer has spread to the bones or other parts of the body, it is rarely cured, but rather treated to shrink, stop, or slow its growth.

The original 3- to 4- week dosing schedule was based mainly on the ability to co-administer these agents with other anticancer agents such as chemotherapy, and for several years there has been increasing interest in de-escalating these agents from 4-weekly to 12-weekly.

The findings of this trial are consistent with those previously reported for de-escalating zoledronate. This trial also included patients receiving de-escalated denosumab and pamidronate. The data presented would suggest that de-escalation of all commonly used BTAs is a reasonable treatment option, and that 12-weekly denosumab is not inferior to the standard of care, according to the authors.

“This study adds to the body of evidence supporting de-escalation as a safe and effective strategy,” said Dr Clemons. “This is great news for patients, oncologists, pharmacists, and health care funders alike.”


1. Clemons MJ, Ong M, Stober C, et al. A randomized trial comparing four-weekly versus 12-weekly administration of bone-targeted agents (denosumab, zoledronate, or pamidronate) in patients with bone metastases from either breast or castration-resistant prostate cancer. J Clin Oncol 37, 2019 (suppl; abstr 11501). Presented at: 2019 ASCO Annual Meeting, May 31-June 4, 2019. Chicago, Illinois.

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