Addition of the oral bisphosphonate ibandronate to endocrine therapy did not significantly improve disease-free survival in patients with early breast cancer, according to the first results from the Dutch TEAM IIb trial presented at the 2016 San Antonio Breast Cancer Symposium.1
Unfortunately we could not confirm our hypothesis that we should treat our patients with ibandronate; however, 73 patients are still using it, so maybe our analysis is a little early.— Sonja Vliek, MD
The results were presented by Sonja Vliek, MD, a medical oncology resident and PhD candidate at the Netherlands Cancer Institute in Amsterdam. “Unfortunately we could not confirm our hypothesis that we should treat our patients with ibandronate; however, 73 patients are still using it, so maybe our analysis is a little early,” she said.
Senior author Sabine Linn, MD, PhD, medical oncologist in the Department of Molecular Pathology at the Netherlands Cancer Institute commented, “We found no proof of additional effects of ibandronate added to adjuvant endocrine treatment at 3 years, but we did see insignificant trends toward improved disease-free survival and fewer bone metastases in the ibandronate arm.”
At a press briefing, Dr. Linn focused on the favorable trends observed, rather than the study’s failure to meet the primary endpoint.
“If the results from this trial are considered along with the results from the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) meta-analysis,2 in which a modest benefit of overall survival was observed for postmenopausal women by adding a bisphosphonate to standard adjuvant systemic therapy, the evidence to treat postmenopausal women with early breast cancer with adjuvant bisphosphonate increases,” she said.
If a patient already has a very good prognosis, the absolute benefit from [ibandronate] will be minimal.— Sabine Linn, MD, PhD
The TEAM IIb study enrolled 1,116 postmenopausal women with hormone receptor–positive early breast cancer who underwent surgery followed by radiotherapy (with or without chemotherapy). They all received adjuvant endocrine therapy for 5 years (tamoxifen followed by exemestane or 5 years of exemestane) and then were randomly assigned concurrently to 3 years of ibandronate at 50 mg/d or no ibandronate.
“We designed the trial 10 years ago. Our objective was to investigate the efficacy of ibandronate, which was a new class of bisphosphonates at the time and was 100 times more potent than clodronate,” Dr. Linn explained.
Patients will be followed for 10 years. The current analysis was performed at a median follow-up of 4.6 years, at which time 3-year disease-free survival was 94.3% for patients receiving ibandronate and 90.8% for those receiving endocrine therapy alone (hazard ratio [HR] = 0.80; 95% confidence interval [CI] = 0.58–1.10; P = .163). The 3.5% absolute difference in events and the relative risk reduction of 20% were not statistically significant.
At 3 years there were 149 disease-free survival events (eg, recurrence, death, other cancer), including 48 deaths in the ibandronate arm and 47 in the control arm (all causes). There were 17 and 29 breast cancer deaths, respectively, and 14 and 9 secondary malignancies.
There was a nonsignificant trend for fewer bone metastases as first events in the ibandronate arm (1.2% vs 3.1%; HR = 0.59; 95% CI = 0.30–1.14; P = .117), she added.
“Is it too early to draw conclusions?” Dr. Vliek questioned, citing several factors that may have affected the outcomes. They include the slow recruitment of patients, resulting amendment of the protocol, and possible lack of statistical power; as well as the early follow-up time. Moreover, 21 women randomized to ibandronate did not take it, and only 67% of patients adhered to treatment. It is possible the drug’s effect was underestimated in this study, she said.
Putting the results into perspective, Dr. Linn told journalists that in the Netherlands, the drug is used selectively. “The debate is whether bisphosphonates should be used in all patients with breast cancer or in just those at higher risk. If a patient already has a very good prognosis, the absolute benefit from this drug will be minimal,” she noted. “You have to weigh the costs and benefits.”
In her presentation, Dr. Vliek noted that “the treatment seemed safe; however, 20% of patients stopped because of side effects.” The most frequent adverse event was gastrointestinal reflux, which was experienced by 2.2% of the control group and 8.6% of the ibandronate group. In addition, four patients (0.7%) in the ibandronate arm developed osteonecrosis of the jaw; complaints resolved in all cases after treatment. Renal function was stable on ibandronate. ■
Disclosure: Dr. Linn has a financial relationship with Roche. Dr. Vliek reported no potential conflicts of interest.
1. Vliek SB, Meershoek-Klein Kranenbarg E, van Rossum AGJ, et al: The efficacy and safety of the addition of ibandronate to adjuvant hormonal therapy in postmenopausal women with hormone receptor-positive early breast cancer. 2016 San Antonio Breast Cancer Symposium. Abstract S6-02. Presented December 9, 2016.