Where Are We With Bone-Targeted Agents in Breast Cancer?

Adam M. Brufsky, M.D., Ph.D., discusses bone-targeted agents in breast cancer, and what we can expect for the future of this kind of therapy.
While providing an update on bone-targeted agents at the 2017 Miami Breast Cancer Conference, Adam M. Brufsky, M.D., Ph.D., emphasized that some bone-targeted agents should be used more frequently, as long as patients and providers are aware of patient conditions and their potential for osteonecrosis.

Brufsky said Xgeva (denosumab) showed a disease-free survival benefit in postmenopausal women with early hormone receptor-positive breast cancer in the Austrian Breast and Colorectal Cancer Study Group-18 (ABCSG-18) trial. Xgeva was given to women who had received aromatase inhibitor (AI) therapy. From 2006 to 2013, the trial enrolled 3,425 patients, of whom 3,420 were randomly assigned to receive Xgeva at 60 mg (1,711 patients) or placebo (1,709 patients) subcutaneously every six months. Xgeva reduced the rate of fracture in women by 50 percent compared with placebo.

Given the damage that adjuvant endocrine therapy can do to bone health in breast cancer patients, these findings may change clinical practice, said Brufsky, associate chief of the Division of Hematology/Oncology and co-director of the Comprehensive Breast Care Center, University of Pittsburgh.

The follow-up analysis of the benefits of adding Xgeva to AI therapy showed that Xgeva also reduces the risk of breast cancer recurrence and death in postmenopausal women.

In an interview with CURE, Brufsky discussed considerations for using the bone-targeted agents Xgeva and Zometa (zoledronic acid) in patients with breast cancer.

What is new in bone-targeted therapies?

Based on meta-analysis studies, there are a number of bone-targeted agents in the postmenopausal setting that have demonstrated a 3 percent improvement in overall survival in patients with breast cancer at 10 years. The real question is, why do we not use them? There are clearly good data available and the questions revolve around which one do we use, how frequently we use it, and for how long. In my opinion, anywhere from two to five years in the meta-analysis seems to be the right amount.

There are some randomized trials that seem to provide a disease-free survival benefit such as with Xgeva, which is a little bit different than the bisphosphonates. The ABCSG-18 trial gave us a very nice result that we need to talk about as a group of breast cancer physicians. Hopefully, we’ll come to some sort of consensus as to how these drugs should be used.

What is the current standard of care for patients with bone metastases?

When managing the patient with bone metastases, there are a number of therapies to consider. If the patient is ER-positive, consider using estrogen-receptor therapy. If the patient is triple-negative, oncologists will most likely treat with chemotherapy. If the patient is HER2-positive, consider using a combination of Herceptin (trastuzumab) plus Perjeta (pertuzamab). But more importantly, oncologists should be using a bone-targeted agent, either Xgeva or Zometa.

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