Adding ibandronate to adjuvant endocrine therapy (ET) provides no long-term benefits for postmenopausal patients with estrogen receptor (ER)-positive breast cancer, according to results of a phase 3 trial published in the Journal of Clinical Oncology.

Three years of daily oral ibandronate did not prolong disease-free survival (DFS) or reduce bone recurrences at 8.5 years of follow-up, researchers found.

Although adjuvant bisphosphonate treatment has shown modest benefits in postmenopausal patients with breast cancer, the efficacy of oral nitrogen-containing bisphosphonates such as ibandronate was unclear. 


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In the phase 3 TEAM-IIB trial, researchers investigated the efficacy and safety of adding daily oral ibandronate to adjuvant ET in postmenopausal patients with stage I-III, ER-positive breast cancer. The study enrolled 1116 patients, 551 who were randomly assigned to receive ET alone for 5 years and 565 who were randomly assigned to receive ET for 5 years plus ibandronate for 3 years. At baseline, the patients’ median age was 62 years, 10% of patients had HER2-positive breast cancer, and 56% received chemotherapy.

At a median follow-up of 8.5 years, there was no significant difference between the ibandronate and control arms for DFS (hazard ratio [HR], 0.97; 95% CI, 0.76-1.24; P =.811), bone recurrence (HR, 0.83; 95% CI, 0.55-1.25), or OS (HR, 1.10; 95% CI, 0.82-1.98; P =.517). 

The researchers noted that ibandronate appeared to confer a DFS benefit and reduce bone recurrences at 3 years, but there were no significant differences between the treatment arms with longer follow-up. At 3 years, the DFS rate was 94% in the ibandronate arm and 91% in the control arm. At 8 years, the DFS rate was 79% in both arms. 

At 3 years, the cumulative incidence of bone recurrences was 2% in the ibandronate arm and 4% in the control arm. At 8 years, the incidence was 7% and 8%, respectively. At 3 years, the OS rate was 98% in the ibandronate arm and 97% in the control arm. At 8 years, the OS rate was 86% and 87%, respectively.

In all, 17% of patients discontinued ibandronate early due to adverse events (AEs). Patients in the ibandronate arm were more likely than those in the control arm to experience gastrointestinal AEs (16% and 10%, respectively; P <.003) and develop osteonecrosis (12 events vs 1 event; P =.002). Patients in the ibandronate arm were less likely than those in the control arm to develop osteoporosis and osteopenia (6% and 11%, respectively; P =.004).

“It is still an unresolved question which is the optimal class, dose, schedule, and treatment duration of bisphosphonates, and which postmenopausal patients should be selected for bisphosphonate treatment. TEAM-IIB study results suggest that 3-year daily ibandronate should not be the recommended strategy,” the researchers concluded.

Disclosures: This research is supported by Roche Nederland B.V. and Pfizer Nederland B.V. through unrestricted research grants. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Vliek SB, Noordhoek I, Meershoek-Klein E, et al. Daily oral ibandronate with adjuvant endocrine therapy in postmenopausal women with estrogen receptor-positive breast cancer (BOOG 2006-04): Randomized phase III TEAM-IIB trial. J Clin Oncol. Published online April 20, 2022. doi:10.1200/JCO.21.00311