Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

De-escalation of Commonly Used Bone-Treating Agents Is A Reasonable Treatment Option for Patients with Bone Metastases from Breast Cancer

The frequency of administration of bone-treating agents did not affect Quality of Life outcomes
02 May 2019
Supportive and Palliative Care
Breast Cancer

De-escalation of commonly used bone-targeting agents (BTAs) such as denosumab, zoledronate and pamidronate is a reasonable treatment option in patients with breast cancer, according to findings presented at the ESMO Breast Cancer 2019, held 2 to 4 May in Berlin, Germany. 

The REaCT-BTA randomised trial compared the non-inferiority of 12-weekly versus 4-weekly BTAs in patients with breast and prostate cancer.

Mark Clemons, Department of Medicine, Division of Medical Oncology, The Ottawa Hospital Regional Cancer Centre, in Ottawa, Canada discussed findings from the breast cancer cohort of the study that was designed to determine the optimal dosing interval of BTAs, including denosumab and bisphosphonates.

Women with breast cancer were elegible if they were BTA-naïve or already being treated with denosumab, zoledronate, or pamidronate. The 160 patients were randomly assigned 1:1 to receive their chosen BTA on a 12-week or 4-week schedule for one year.

The primary endpoint was Health Related Quality of Life (HRQoL), as assessed using the EORTC Quality of Life Questionnaire (QLQ)-C30 Functional Domain-Physical Subdomain. Secondary endpoints included: pain, according to the EORTC-QLQ-BM22-pain domain, Global Health Status by the EORTC-QLQ-C30 and symptomatic skeletal event (SSE) rates, which was calculated as the cumulative incidence of SSEs, accounting for death as a competing risk. Adverse events and toxicity were also compared between the two regimens.

Both treatments provided similar Quality of Life, Global Health Status and pain scores

The 12-week treatment group comprised 79 (49.4%) patients, and 81 (50.6%) patients received a BTA on a 4-weekly basis. In both groups, 64 (40%) patients were BTA-naïve. Sixty (37.5%) patients were treated with denosumab, 48 (30%) received zoledronate, and 52 (32.5%) patients received pamidronate.

With the 12- and 4-weekly regimens, the reported outcomes showed no significant difference in change from baseline regarding HRQoL, pain, or Global Health Status.

The change in HRQoL-physical domain median scores were 0 (range, -87 to 20] in the 12-weekly arm compared to 0 (range, -60 to 60) in the 4-weekly arm, and the median QLQ-BM-pain scores were 0 (range, -80 to 33) compared to 0 (range, -27 to 20), respectively. The median change in Global Health Status scores were also the same in the respective treatment arms; the median QLQ-C30 was 0 (range, -67 to 50) versus 0 (range, -50 to 50) in the 12- and 4-weekly treatment arms, respectively.

No difference in SSE rates were reported

SSEs rates at 48 weeks occurred in 9 (11%) of patients on the 12–week schedule and 7 (9%) patients receiving BTAs every 4 weeks (p = 0.42).

Cumulative Incidence of SSE

Cumulative incidence of symptomatic skeletal events. - © Mark Clemons.  

Changes in dosing schedules occurred less often in the 12-week versus the 4-week arm; 17% of patients versus 31% of patients in the respective arms had dosing changes.

The results were also similar for subgroup analyses across the BTA naïve and pre-treated groups, as well as for patients receiving denosumab, zoledronate, or pamidronate.


Based upon these findings, the authors noted that these results were consistent with those previously reported for de-escalating zoledronate, although this trial also included patients receiving de-escalated denosumab and pamidronate.

The overall results of the REaCT-BTA trial are pending; however, the data presented at this congress suggest that de-escalation of commonly used BTAs is a reasonable treatment option.


Funding for this study was provided through Canadian Institutes of Health Research-SPOR funding, Cancer Care Ontario (Government of Ontario), and the Ottawa Hospital Foundation.



LBA 3 – Clemons M, Stober C, Mates M, et al. A pragmatic, randomised, multicentre trial comparing 4-weekly vs. 12-weekly administration of bone-targeted agents (denosumab, zoledronate or pamidronate) in patients with bone metastases. ESMO Breast Cancer 2019; 1-2 May, Berlin, Germany.

Last update: 02 May 2019

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.