Kefah Mokbel, Chair of Breast Cancer Surgery at London Breast Institute and Honorary Professor of Medicine at Cardiff University School of Medicine, shared a post on LinkedIn:
”One Dose Is Enough:
5-Year Data Back a Single 4 mg Zoledronate Infusion in Early Breast Cancer
Final 5-year results from the REaCT-ZOL randomized trial (NEJM Evidence, May 2026) support a meaningful shift in adjuvant bisphosphonate practice for postmenopausal early breast cancer.
211 postmenopausal patients with early breast cancer were randomized to:
- A single 4 mg IV zoledronate infusion, or
- 4 mg IV zoledronate every 6 months for 3 years (6 doses total)
5-year outcomes (single dose vs. 6-monthly):
- Recurrence-free survival: 88.7% vs. 84.1% (HR 0.71; 95% CI 0.34–1.51)
- Bone metastasis–free survival: 90.6% vs. 86.0% (HR 0.68; 95% CI 0.30–1.52)
- Overall survival: 91.6% vs. 88.0% (HR 0.79; 95% CI 0.34–1.82)
- Osteonecrosis of the jaw: 0% vs. 0%
- Fragility fractures: 5% vs. 2%
Oncological outcomes were closely comparable between the two schedules. Combined with the previously reported 3-year data showing greater patient convenience, less toxicity, and lower treatment discontinuation with a single infusion, the totality of evidence makes a single 4 mg infusion the better option over 6-monthly dosing for 3 years.
Why this matters:
Adjuvant bisphosphonate therapy is an established survival-improving intervention in postmenopausal early breast cancer, yet the optimal schedule and cumulative dose have never been clearly defined. REaCT-ZOL provides direct randomized evidence that a single 4 mg infusion delivers equivalent oncological benefit with substantially less burden – fewer hospital visits, lower toxicity exposure, reduced healthcare costs, and improved adherence.
The trial is modest in size and confirmatory data from larger studies remain valuable, but for clinicians and patients weighing pragmatic, patient-centred regimens, this is a clinically meaningful step toward sensible de-escalation.
More is not always better – even for our most established adjuvant therapies.”
Title: Every Six-Month versus Single-Dose Adjuvant Zoledronate in Early Breast Cancer
Authors: Mark Clemons, Carol Stober, Gregory R. Pond, Henry Conter, Demetrios Simos, Sukhbinder Dhesy-Thind, Mihaela Mates, Mateya Trinkaus, John Hilton, Marie-France Savard, Dean Fergusson, Lisa Vandermeer, Arif Ali Awan
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