San Antonio Breast Cancer Symposium

San Antonio Breast Cancer Symposium

Perspective from Amy H. Comander, MD
December 09, 2016
5 min read
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Addition of ibandronate to adjuvant hormonal therapy shows no benefit in early breast cancer

Perspective from Amy H. Comander, MD
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SAN ANTONIO — The addition of ibandronate to adjuvant hormonal therapy demonstrated no proof of benefit for postmenopausal women with early hormone receptor–positive breast cancer, according to results of the TEAM IIb trial presented at San Antonio Breast Cancer Symposium.

However, the ibandronate regimen showed a trend toward longer DFS and less bone metastases.

Sabine Linn

“It might be that this analysis was done too early, especially for this type of breast cancer,” Sabine Linn, MD, PhD, medical oncologist in the department of molecular pathology at Netherlands Cancer Institute, said during a press conference. “For luminal A breast cancer, once might need a more mature follow-up to see the true effect of the addition of ibandronate. The other question is whether this study was underpowered.”

Prior research established a clear interaction between tumor cells and bone. Osteoclasts are involved in bone breakdown. When they are active, they release several growth factors from bone that help tumor cells to grow and proliferate. In turn, tumor cells release growth factors that further stimulate osteoclasts to become more active.

Bisphosphonates can block the activity of osteoclasts, breaking this vicious cycle.

The TEAM IIb trial included 1,116 postmenopausal women with early-stage breast cancer treated at one of 37 hospitals in the Netherlands.

All women received 5 years of hormonal therapy with tamoxifen followed by exemestane, or exemestane without a switch. Linn and colleagues randomly assigned half the women to also receive 3 years of treatment with the bisphosphonate ibandronate (Boniva, Genentech), administered in 50-mg daily doses.

DFS at 3 years served as the primary endpoint. Safety, OS, time to bone metastasis and other sites of recurrence served as secondary endpoints.

Trial protocol established a 10-year follow-up. Linn presented initial data based on median follow-up of 4.6 years.

During that time, 149 DFS events occurred. Researchers reported 95 deaths during follow-up (ibandronate, n = 48; control, n = 47). Seventeen deaths (35.4%) in the ibandronate group and 29 deaths (61.7%) in the control group were due to breast cancer; 14 patients (29.2%) assigned ibandronate and nine (19.1%) assigned the control regimen died of secondary malignancy.

At 3 years, researchers reported a higher DFS rate (94.3% vs. 90.8%; HR = 0.8; 95% CI, 0.58-1.1) and reduced incidence of bone metastasis (1.6% vs. 4.7%; HR = 0.65; 95% CI, 0.38-1.11) in the ibandronate group. However, the differences did not reach statistical significance.

Incidence of stomach- or reflux-related symptoms was higher in the ibandronate group (8.3% vs. 2.2%). Twenty percent of patients assigned the experimental regimen discontinued treatment due to side effects, but not all were related to ibandronate.

Four patients (0.7%) developed osteonecrosis of the jaw, but all cases resolved after treatment ended.

Renal function appeared stable during ibandronate treatment. Two patients developed renal failure, but the condition may not have been related to treatment, Linn said.

“If the results from this trial are considered along with the results from the EBCTCG trial, in which a modest benefit of OS 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,” Linn said in a press release. “Patients should discuss this adjuvant treatment with their physicians to outweigh the possible side effects from the possible gain in survival.” – by Mark Leiser

Reference:

Linn S, et al. Abstract 6-02. Presented at: San Antonio Breast Cancer Symposium; Dec. 6-10, 2016; San Antonio.

Disclosure: The study was funded by unrestricted research grants from Roche Netherlands and Pfizer Netherlands. Linn reports research grants from Roche Netherlands and an advisory board role with Roche.