Adjuvant Ibandronate Does Not Improve Survival in HR-Positive Early Breast Cancer

Phoebe Starr

Breast Cancer

San Antonio, TX—The addition of the oral bisphosphonate ibandronate (Boniva) to endocrine therapy after surgery for hormone receptor (HR)-positive, early-stage breast cancer in early postmenopausal women did not significantly improve overall survival or disease-free survival (DFS), according to results of a study presented at the 2016 San Antonio Breast Cancer Symposium.

Sabine C. Linn, MD, PhD, Group Leader, Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, said that the study was unlikely to change current practice, and US experts agreed that bisphosphonates are generally reserved for women at high risk for fracture.

“There is no proof of an additional effect of ibandronate at 3 years when added to endocrine therapy. However, a trend was seen toward improved disease-free survival with an absolute benefit of 3.5% favoring ibandronate and fewer bone metastasis developed in patients on the ibandronate arm, but the incidence of bone metastasis was low. It may be that 3 years is too early to see an effect,” Dr Linn said.

“In the Netherlands, it is clinical practice to use this drug in high-risk postmenopausal women with early-

stage breast cancer. The debate is whether we should use it in all patients with breast cancer or just in those with higher risk. If a patient already has a very good prognosis, the absolute benefit from this drug will be minimal. You have to weigh the costs and benefits,” she pointed out.

Study Results

The TEAM IIb trial randomized 1116 postmenopausal women with early HR-positive breast cancer and no evidence of metastasis who had undergone surgery plus or minus radiation and/or chemotherapy to adjuvant endocrine therapy for ≥5 years—tamoxifen (Nolvadex) followed by exemestane (Aromasin), or exemestane alone—or adjuvant endocrine therapy for ≥5 years plus 3 years of ibandronate 50 mg daily. The planned follow-up is 10 years.

Dr Linn reported the first results of 3-year DFS. At 3 years, only 67% of patients were still taking ibandronate, and 20 patients never started taking it. Accrual was slow from 2007 to 2014, she said.

There were 47 deaths in the control group and 48 in the ibandronate-treated group. In the control arm, 29 (61.7%) deaths were breast cancer–specific compared with 17 (35.4%) in the ibandronate arm. The rate of death because of secondary malignancy was higher in the ibandronate arm—9 (19.2%) for controls and 14 (29.2%) for ibandronate.

The primary end point, 3-year DFS, was 94.3% in the ibandronate arm versus 90.8% for controls, a difference that was not significant. A nonsignificant 35% reduction in bone metastasis was observed, with 23 (4.7%) events in the control arm and 8 (1.6%) events in the ibandronate arm.

Ibandronate was associated with more adverse events, particularly gastrointestinal symptoms (2.2% in the control arm vs 8.3% of ibandronate-treated patients). Approximately 20% of ibandronate-treated patients stopped taking the drug because of side effects, not all of which were attributed to the drug. Renal function remained stable during ibandronate treatment, and osteonecrosis of the jaw—a dreaded side effect of bisphosphonates—occurred in 4 (0.7%) patients receiving ibandronate, but appeared to resolve once treatment was stopped.

The US Point of View

The practice in the United States is to check the patient’s bone mineral density before deciding whether to add a bisphosphonate as treatment for early-stage breast cancer, noted Sara A. Hurvitz, MD, Medical Director, Clinical Research Unit, Los Angeles Jonsson Comprehensive Cancer Center, Santa Monica, CA. “We see women who are going on aromatase inhibitors who have moderate-to-severe osteopenia or osteoporosis and then have more impetus to use a bisphosphonate. We sell it to them as a 2-for-1 benefit protecting bone health and possibly improving their long-term survival,” Dr Hurvitz said.

Dr Hurvitz noted that some patients are afraid of the side effects of bisphosphonates, especially osteonecrosis of the jaw—a fear fueled by what they read on the Internet. “We have to inform them about the risks of these drugs, even though the risk of osteonecrosis is small,” she said.

Another breast cancer expert from the United States, Mothaffar F. Rimawi, MD, Medical Director, Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, said that bisphosphonates may be under-­used in early breast cancer, although they are indicated to prevent aromatase inhibitor–induced bone loss. “Because of physician or patient anxiety, the drugs are not used as often,” Dr Rimawi said.