Extending adjuvant treatment with zoledronate beyond 2 years did not improve survival in patients with high-risk early breast cancer, according to results of a study published in JAMA Oncology.
Although adjuvant bisphosphonates are used to treat postmenopausal patients with early breast cancer, the optimal duration of treatment is unclear, the study authors noted.
In the phase 3 SUCCESS A trial (ClinicalTrials.gov Identifier: NCT02181101), the authors compared 5 years of adjuvant zoledronate with 2 years of adjuvant zoledronate in patients with early breast cancer.
The study enrolled 3754 patients with node-positive or high-risk node-negative disease, and 2987 of them were evaluable. The patients’ median age at baseline was 53 years (range, 21-86 years).
Patients first received 3 cycles of treatment with fluorouracil, epirubicin, and cyclophosphamide. They were then randomly assigned to 3 cycles of docetaxel with or without gemcitabine. After chemotherapy, the patients were randomly assigned to receive 5 years or 2 years of treatment with zoledronate.
Multivariable analyses showed no significant differences in outcomes between the 5-year and 2-year treatment arms. There were no differences in disease-free survival (hazard ratio [HR], 0.97; 95% CI, 0.75-1.25; P =.81), overall survival (HR, 0.98; 95% CI, 0.67-1.42; P =.90), or distant disease-free survival (HR, 0.87; 95% CI, 0.65-1.18; P =.38).
In addition, there was no significant between-arm difference in the presence of circulating tumor cells at 5 years (x2 test, P =.14).
Adverse events (AEs) were more frequent in the 5-year arm (46.2%) than in the 2-year arm (27.2%). The most common skeletal-related AEs (in the 5-year and 2-year arms, respectively) were bone pain (8.3% vs 3.7%) and arthralgia (5.1% vs 3.1%).
Osteonecrosis of the jaw was more common in the 5-year arm (11 patients) than in the 2-year arm (5 patients).
“The results of this phase 3 randomized clinical trial indicate that extending the zoledronate treatment beyond 2 years does not improve the prognosis of high-risk patients with early breast cancer receiving chemotherapy, suggesting that the currently recommended bisphosphonate treatment duration of 3 to 5 years could be reduced,” the study authors wrote.
Disclosures: This research was supported by AstraZeneca, Chugai, Menarini Silicon Biosystems, Lilly, Novartis, and Sanofi-Aventis. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Friedl TWP, Fehm T, Müller V, et al. Prognosis of patients with early breast cancer receiving 5 years vs 2 years of adjuvant bisphosphonate treatment: a phase 3 randomized clinical trial. JAMA Oncol. Published online June 24, 2021. doi:10.1001/jamaoncol.2021.1854