“Appropriately selected postmenopausal women with breast cancer warrant consideration for adjuvant bisphosphonate therapy, according to an updated clinical guideline.
“Either zoledronic acid (Zometa) or clodronate may be considered for adjuvant therapy, as data supporting use of other bisphosphonates remain limited. The RANK ligand-targeted monoclonal antibody denosumab (Xgeva) did not make the cut as recommended therapy because of a lack of long-term survival data to support its use.
” ‘Data for adjuvant denosumab look promising but are currently insufficient to make any recommendation,’ concluded a panel of experts representing the American Society of Clinical Oncology (ASCO) and Cancer Care Ontario.”
“As people age, the risk of fracturing a bone – whether it’s a hip, a wrist, vertebrae, an ankle or toe, climbs steadily. For women and men who live after a cancer diagnosis, the risk of breaking bone is greater.
“At this year’s San Antonio Breast Cancer Symposium, Dr. Michael Gnant of Vienna gave an update on a major trial of denosumab in its capacity to reduce fractures and possibly stave off metastases. This drug is manufactured and sold by Amgen in a low-dose form as Prolia. Prolia is a monoclonal antibody that doesn’t require intravenous administration; it’s injected under the skin, just twice each year.
“The ongoing trial, by the Austrian Breast and Colorectal Cancer Study Group (ABCSG), includes over 3,400 postmenopausal women with non-metastatic, hormone receptor positive breast cancer. All participants took an aromatase inhibitor, a standard treatment given to lower hormone levels, and were randomized to receive either low-dose (60 milligrams) denosumab or a placebo injection under the skin, twice yearly.”
“In a phase III trial (ABCSG-18) reported in The Lancet, Gnant et al found that adjuvant denosumab (Xgeva) reduced the risk of clinical fracture in women with breast cancer receiving aromatase inhibitor therapy.
“In the double-blind study, 3,420 women from Austria and Sweden with early hormone receptor–positive breast cancer receiving aromatase inhibitors were randomized between December 2006 and July 2013 to receive subcutaneous denosumab 60 mg (n = 1,711) or placebo (n = 1,709) every 6 months.
“The primary endpoint was time to first clinical fracture on intention-to-treat analysis. Patients were treated until the prespecified number of 247 first clinical fractures was reached.
“Patients had a median age of 64 years. At baseline, 55% had normal total lumbar spine bone mineral density (T score ≥ –1.0), and the remainder had T scores lower than –1.0. Overall, 16% of patients started aromatase inhibitor therapy at the time of randomization, with the remainder having been on treatment for a median of 1 month prior to randomization. In total, 25% of patients had also received (neo)adjuvant chemotherapy.”
“One bone-preserving drug is as good as another in early stage breast cancer, a researcher said here.
“In a large randomized trial, there were few differences in anti-cancer efficacy among three different members of the bisphosphonate class, according to Julie Gralow, MD, of the University of Washington in Seattle.
“Amgen AMGN 0.49% today announced results from a randomized, double-blind, placebo-controlled, multicenter Phase 3 study evaluating the treatment effect of adjuvant Prolia® (denosumab), 60 mg once every six months, therapy in postmenopausal women with early hormone receptor positive (HR+) breast cancer receiving aromatase inhibitor therapy. The trial met its primary endpoint of time from randomization to first clinical fracture (HR=0.5, 95 percent CI 0.39-0.65, p<0.0001). The observed 50 percent reduction in fractures between the Prolia and placebo arms, 92 versus 176, respectively, was similar in patients with normal bone health at baseline (n=1,872, HR=0.44, p<0.0001) and in patients who started the trial with early signs of bone loss (n=1,548, HR=0.57, p=0.0021). The data will be presented at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago today at 9:12 a.m. CT (abstract no. 504). In addition to the presentation, the paper was published online by The Lancet.
“This is the first Prolia trial to enroll patients independent of baseline bone mineral density (BMD) and with the majority in the normal BMD range. The study, which enrolled a total of 3,425 patients, was conducted by the Austrian Breast and Colorectal Cancer Study Group (ABCSG).
” ‘Fracture is a common side effect of aromatase inhibitors, which are an important first-line therapy for postmenopausal women with non-metastatic breast cancer,’ said principal investigator Michael Gnant, professor of surgery at Medical University of Vienna. ‘These encouraging data demonstrate the potential benefit of initiating Prolia simultaneously with aromatase inhibitor therapy, regardless of the patient’s baseline BMD, to decrease the risk of fracture.’ “