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Randomized Controlled Trial
. 2024 Dec;208(3):523-533.
doi: 10.1007/s10549-024-07443-2. Epub 2024 Jul 31.

A randomised trial comparing 6-monthly adjuvant zoledronate with a single one-time dose in patients with early breast cancer

Arif Ali Awan  1   2 , Carol Stober  2 , Gregory R Pond  3 , Igor Machado  1 , Lucas Clemons  2 , Henry Conter  4 , Demetrios Simos  5 , Sukhbinder Dhesy-Thind  3 , Mihaela Mates  6 , Vikaash Kumar  7 , John Hilton  1   2 , Marie-France Savard  1   2 , Dean Fergusson  8 , Lisa Vandermeer  2 , Mark Clemons  9   10   11 ; REaCT Investigators
Affiliations
Randomized Controlled Trial

A randomised trial comparing 6-monthly adjuvant zoledronate with a single one-time dose in patients with early breast cancer

Arif Ali Awan et al. Breast Cancer Res Treat. 2024 Dec.

Abstract

Purpose: While adjuvant bisphosphonate use in early breast cancer (EBC) is associated with improvements in breast cancer-specific outcomes, questions remain around optimal bisphosphonate type, dose and scheduling. We evaluated a single zoledronate infusion in a prospective randomised trial.

Methods: Postmenopausal patients with EBC were randomised to receive a single infusion of zoledronate (4 mg IV) or 6-monthly treatment for 3 years. Outcomes measured were; Quality of Life (QoL; EQ-5D-5L), bisphosphonate-related toxicities, including acute phase reactions (APRs), recurrence-free survival (RFS), bone metastasis-free survival (BMFS) and overall survival (OS).

Results: 211 patients were randomized to either a single infusion (n = 107) or six-monthly treatment (n = 104). After 3 years of follow up there were no significant differences between the arms for QoL and most toxicity endpoints. APRs following zoledronate occurred in 81% (171/211) of patients (77.6% in single infusion arm and 84.6% in the 6-monthly group). While the frequency of APRs decreased over 3 years in the 6-monthly arm, they still remain common. Of 34/104 (32.7%) patients who discontinued zoledronate early in the 6-monthly treatment group, the most common reason was APRs (16/34, 47%). At the 3 year follow up, there were no differences between arms for RFS, BMFS or OS.

Conclusion: A single infusion of zoledronate was associated with increased patient convenience, less toxicity, and lower rates of treatment discontinuation. Despite the common clinical impression that APRs decrease with time, this was not observed when patients were specifically questioned. While the study is not powered for non-inferiority, longer-term follow-up for confirmation of RFS and OS rates is ongoing.

Keywords: Adjuvant; Bisphosphonates; Breast cancer; Zoledronate.

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Conflict of interest statement

Clemons and Dhesy-Thind reported serving on the CCO-ASCO guideline committee. Conter reported being an employee of F. Hoffmann-La Roche AG. No other disclosures were reported.

Figures

Fig. 1
Fig. 1
Consort flow diagram
Fig. 2
Fig. 2
Incidence of acute phase reaction (APRs) following zoledronate infusions
Fig. 3
Fig. 3
3 Year recurrence-free survival (RFS), bone metastasis-free survival (BMFS) and overall survival (OS) rates
See this image and copyright information in PMC

References

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