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30-06-2021 | Oncology | News | Article

Zoledronate treatment duration ‘could be reduced’ for early breast cancer

Author: Laura Cowen

medwireNews: Extended adjuvant treatment with zoledronate offers no survival benefit compared with a 2-year treatment course for people with high-risk early breast cancer, suggest results of the phase 3 SUCCESS A trial.

Writing in JAMA Oncology, Thomas Friedl (University Hospital Ulm, Germany) and co-authors say their findings indicate “that the currently recommended bisphosphonate treatment duration of 3 to 5 years could be reduced.”

The study included 2987 participants (median age 53 years) with either node-positive or high-risk node-negative (tumor size ≥pT2, histologic grade 3, hormone receptor-negative, or age ≤35 years) primary invasive breast cancer who all underwent primary breast-conserving surgery or modified radical mastectomy.

Initially, the patients were randomly assigned to receive adjuvant chemotherapy with three cycles of fluorouracil, epirubicin, and cyclophosphamide followed by three cycles of docetaxel with or without gemcitabine.

After chemotherapy, patients were again randomly assigned to receive intravenous zoledronate for 5 years (n=1540) or 2 years (n=1447). Both groups received 4 mg every 3 months for the first 2 years, then those in the 5-year group continued with 4 mg every 6 months for a further 3 years.

The researchers report that, during approximately 3 years of follow-up, beginning 2 years after the start of zoledronate treatment, there were 250 disease-free survival (DFS) events, including 116 deaths.

In both univariable and multivariable analyses, there was no significant difference in DFS, distant DFS, or overall survival between the participants who received zoledronate for 5 years and those who received it for 2 years.

Subgroup analyses for DFS showed similar results, with no significant differences between the two zoledronate durations by menopausal status, surgery type, hormone receptor status, or tumor characteristics. And there was no difference between the two groups in the number of bone recurrence events, at 25 and 28 in the 5-year and 2-year arms, respectively.

There were, however, significantly more adverse events (AEs) of any grade with 5 years of zoledronate versus 2 years (46.2 vs 27.2%) as well as more grade 3 or 4 AEs (7.6 vs 5.1%). Bone pain (8.3 vs 3.7%) and arthralgia (5.1 vs 3.1%) were the most common events in both groups, but were less common with 2 years of treatment, as were fractures (0.9 vs 0.2%) and osteonecrosis of the jaw (0.7 vs 0.3%)

Friedl et al conclude: “Our results suggest that extended adjuvant bisphosphonate treatment with zoledronate for 5 years should not be considered in patients with [early breast cancer] in the absence of decreased bone density.”

In an accompanying editorial, Ian Tannock (University of Toronto, Ontario, Canada) and co-authors say that although the SUCCESS A study had some limitations, such as the inclusion of premenopausal women not receiving ovarian suppression and the low event rates, these are unlikely to have made “a substantial difference” to the outcomes.

They therefore ask: “In light of this, and the modest outcomes of bisphosphonates compared with no bone-targeted therapy in historical trials, an important question needs to be answered: in a contemporary breast cancer setting in which DFS events are infrequent, what, if any, is the benefit from adjuvant bisphosphonates?”

And they conclude: “It is time to reevaluate the guidelines.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group

JAMA Oncol 2021; doi:10.1001/jamaoncol.2021.1854
JAMA Oncol 2021; doi:10.1001/jamaoncol.2021.1516