In the Dutch phase III TEAM-IIB trial reported in the Journal of Clinical Oncology, Sonja B. Vliek, MD, and colleagues found that the addition of oral ibandronate to adjuvant endocrine therapy did not improve disease-free survival in postmenopausal women with estrogen receptor (ER)-positive stage I to III breast cancer.

Sonja B. Vliek, MD

Study Details

In the open-label, multicenter trial, 1,116 patients were randomly assigned between February 2007 and May 2014 to receive adjuvant endocrine therapy with daily ibandronate at 50 mg once daily for 3 years (n = 565) or endocrine therapy alone (n = 551). Endocrine therapy consisted of tamoxifen at 20 mg once daily for 2 to 3 years followed by exemestane at 25 mg once daily for 2 to 3 years for a total of at least 5 years in patients with HER2-negative disease (approximately 91% of total population), or exemestane monotherapy for 5 years in those with HER2-positive disease.

The primary endpoint was disease-free survival in the intention-to-treat population.

Disease-Free Survival

Median follow-up was 8.5 years (interquartile range = 7.1–10.0 years).

No significant difference in disease-free survival was observed for the ibandronate group vs the control group (hazard ratio [HR] = 0.97, 95% confidence interval [CI] = 0.76–1.24, P = .811). Rates at 3, 5, and 8 years were 94% vs 91%, 89% vs 86%, and 79% vs 79%.

No significant differences were observed in:

• Overall survival (HR = 1.10, 95% CI = 0.82–1.49, P = .517), with rates at 3, 5, and 8 years of 98% vs 97%, 93% vs 92%, and 86% vs 87%
• Recurrence-free interval (HR = 0.84, 95% CI = 0.62–1.14), with rates at 3, 5, and 8 years of any recurrence of 3% vs 7%, 7% vs 10%, and 12% vs 14%
• Bone recurrence–free interval (HR = 0.83, 95% CI = 0.55–1.25), with recurrence rates at 3, 5, and 8 years of 2% vs 4%, 3% vs 6%, and 7% vs 8%.

Adverse Events

The most common adverse events of any grade in the ibandronate group through 3.5 years after random assignment were hot flashes (32.6% vs 35.8% in control group), arthralgia (25.7% vs 22.5%), and fatigue (16.5% vs 18.7%). Gastrointestinal adverse events—mainly dyspepsia—were more common in the ibandronate group (16% vs 10%, P = .003). Osteoporosis/osteopenia was more common in the control group (6.4% vs 11.3%, P = .004). In the ibandronate group, 17% of patients discontinued treatment due to adverse events. A total of 12 patients vs 1 patient developed osteonecrosis (P = .002), with 11 patients in the ibandronate group developing osteonecrosis of the jaw.

The investigators concluded, “In postmenopausal women with ER-positive breast cancer, adjuvant ibandronate at 50 mg once daily does not improve disease-free survival and should not be recommended as part of standard treatment regimens.”

Sabine C. Linn, MD, PhD, of the Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Roche Nederland B.V. and Pfizer Nederland B.V. For full disclosures of the study authors, visit ascopubs.org.