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 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.
Conclusions
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.
Disclosure
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.
Reference
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.