Feasibility outcomes of a randomised, multicentre, pilot trial comparing standard 6-monthly dosing of adjuvant zoledronate with a single one-time dose in patients with early stage breast cancer

Arif Awan, Terry Ng, Henry Conter, William Raskin, Carol Stober, Demetrios Simos, Greg Pond, Sukhbinder Dhesy-Thind, Mihaela Mates, Vikaash Kumar, Dean Fergusson, Brian Hutton, Deanna Saunders, Lisa Vandermeer, Mark Clemons, REaCT Investigators, Arif Awan, Terry Ng, Henry Conter, William Raskin, Carol Stober, Demetrios Simos, Greg Pond, Sukhbinder Dhesy-Thind, Mihaela Mates, Vikaash Kumar, Dean Fergusson, Brian Hutton, Deanna Saunders, Lisa Vandermeer, Mark Clemons, REaCT Investigators

Abstract

Background: Adjuvant zoledronate is widely used in patients with early stage breast cancer (EBC), but its optimal duration and dosing interval is still unknown. While a single-dose of zoledronate can improve bone density for many years, a proper evaluation of its effects on breast cancer-related outcomes would require a large trial. In this pilot study we evaluated the feasibility of performing such a trial.

Methods: Eligible patients with EBC were randomised to receive either one dose of zoledronate or 7 doses (6-monthly dosing for 3 years). Feasibility was assessed by a combination of primary outcomes including: activation of at least 6 Ontario sites within a year, active participation (i.e. approaching eligible patients for study participation) of at least half of the medical oncologists, and enrolment of at least 100 patients across all sites within 9 months of the sixth site being activated.

Results: All 6 sites were activated within 1 year and of 47 medical oncologists, 27 (57%) approached patients. Between November 2018 and April 2020, 211 eligible patients were randomised, 106 (50.2%) to a single dose of zoledronate and 105 (49.8%) to 6-monthly dosing. Baseline characteristics of randomised patients included; median age 59 (range 36-88), ER and/or PR positive (85%), Her2 positive (23%), menopausal status (premenopausal [19%], perimenopausal [6.7%] and postmenopausal [74%]) and 74% received neo/adjuvant chemotherapy.

Conclusions: All study feasibility endpoints were met in this trial comparing alternative schedules for adjuvant zoledronate. We will now seek funding for performing a larger efficacy trial.Trial registration: NCT03664687.

Keywords: Adjuvant bisphosphonate; Breast cancer; Zoledronate.

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

© 2020 The Author(s).

Figures

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Fig. 1
CONSORT Diagram.

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