“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.”
“Men with bone-metastatic castration-resistant prostate cancer (mCRPC) appeared to derive additional benefits from treatment with radium-223 with concomitant bone-targeted therapies, according to data from an extended-access program.
“After a median follow-up of 7.5 months from initial injection of radium-223, patients on concomitant denosumab had yet to reach a median overall survival (OS), whereas patients treated with radium-223 alone had a median survival of 13.4 months.”
“TNFSF11, also known as RANKL, shows potential as a genetic pathway in the prevention of breast cancer for women carrying BRCA1 mutations. Early study findings, published in Nature Medicine, show that a drug currently used in the treatment of osteoporosis, denosumab (Xgeva)—an inhibitor of RANKL—could also be used for the prevention and delay of tumor growth for BRCA1-mutation carriers.
“ ‘These findings imply an integral role for the RANK pathway in tumor initiation in BRCA1-mutation carriers and lend support to clinical studies for the “repurposing” of denosumab as a novel preventative therapy strategy in these and possibly other “high-risk” women,’ wrote study authors.”
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“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.”
“A pair of drugs already on the market appear to reduce the recurrence of breast cancer in women who’ve already undergone treatment, two new clinical trials show.
“The chemotherapy drug capecitabine (Xeloda) seems to reduce by nearly a third the risk of breast cancer recurrence if women receive the drug following surgery to remove their cancer, researchers were to report Wednesday at the 2015 San Antonio Breast Cancer Symposium.
“In addition, an osteoporosis medication called denosumab appears to reduce recurrence risk by 18 percent in women who have HR-positive breast cancer, a second study reports.”
“The addition of the bone-targeting drug denosumab to adjuvant hormonal therapy in postmenopausal breast cancer patients improves disease-free survival (DFS), reducing the risk of disease recurrence by 18% compared with placebo, according to the results of the Austrian Breast and Colorectal Cancer Study Group (ABCSG)-18 trial.
“The results (abstract S2-02) were presented at the 2015 San Antonio Breast Cancer Symposium (SABCS), held December 8–12 in San Antonio, Texas.
“ ‘This is a very safe treatment and my clinical conclusion is that denosumab reduces the risk of disease recurrence or death, and this benefit is similar to what bisphosphonates can do and comes in addition to highly significantly reducing clinical fractures,’ said study author and presenter Michael Gnant, MD, professor of surgery at the Medical University of Vienna in Austria, during a press conference. ‘I believe that we should offer this treatment to postmenopausal breast cancer patients on adjuvant aromatase inhibitors.’ “
“A new meta-analysis suggests that de-escalation of bone-targeted agents such as bisphosphonates and denosumab is a safe strategy in patients with bone metastases from breast cancer. There is a growing body of evidence suggesting such de-escalation will soon be considered standard of care.
“Bone-targeted agents are generally given every 3 to 4 weeks beginning at the time of diagnosis of bone metastases, until death. ‘If de-escalation of treatment is as efficacious as 3–4 weekly dosing, it could reduce clinic visits, drug side effects for patients, in addition to reducing costs to both the patient and the health care system,’ wrote study authors led by Mark Clemons, MD, of the Ottawa Hospital Cancer Centre in Canada.
“Clemons and colleagues conducted a systematic review and meta-analysis of published research on de-escalation of bone-targeted agents; six studies reported data for at least one ‘outcome of interest’ involving pamidronate, zoledronate, and denosumab. Results of the analysis were published online ahead of print in Annals of Oncology.
“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.”
“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.’ “