SAN ANTONIO — Adjuvant denosumab appeared to reduce the risk for disease recurrence or death among postmenopausal women with breast cancer, according to study results presented at the San Antonio Breast Cancer Symposium.
Adjuvant endocrine therapy is known to negatively impact bone health among pre- and postmenopausal women with breast cancer, according to study background.
The primary analysis of the ABCSG-18 trial — presented at the 2015 ASCO Annual Meeting — showed 60 mg adjuvant denosumab (Prolia, Amgen) twice yearly significantly reduced the risk for clinical fractures (HR = 0.5; P ˂ .001) and improved bone health without measurable toxicity among postmenopausal women with breast cancer.
“The question remaining is, are we also impacting outcomes of DFS and OS in these patients?” Michael Gnant, MD, professor of surgery at the Medical University of Vienna, said during a press conference. “Following the primary endpoint results, the independent data monitoring committee recommended we offer patients the option of unblinding. … In 2016, we are going to offer all trial patients the option of being unblinded. If they were on placebo, they will be offered the antibody for 3 years.
“However, since this will somewhat compromise the integrity of the blinded outcome data, the recommendation was to do a DFS analysis now based on a time–treatment analysis,” Gnant added.
Researchers defined DFS as time to any evidence of local or distant metastasis, contralateral metastasis, secondary cancer or deaths from any cancer.
The analysis included 3,425 postmenopausal patients (median age, 64 years; range, 38-91) with non-metastatic breast cancer. Seventy-two percent of women had tumors smaller than 2 cm and 71% had node-negative disease. Twenty-five percent of women received neoadjuvant or adjuvant chemotherapy, and all women received an aromatase inhibitor.
After a median follow-up of 4 years, 203 DFS events occurred in the placebo group vs. 167 in the denosumab group. These data equated to a borderline statistically significant difference in the intent-to-treat analysis (HR = 0.81; 95% CI, 0.66-1).
The absolute benefit was 1.2% at 3 years, 2.1% after 5 years and 3.1% at 7 years of follow-up.
Gnant and colleagues then conducted exploratory subgroup analyses. Starting denosumab early, ductal histology (HR=0.79; P = .048) and having both ER- and PR-positive tumors (HR=0.75; P = .013) appeared to drive the denosumab benefit. Further, a significantly greater proportion of women with tumors larger than 2 cm (n = 946) achieved 7-year DFS when they received denosumab vs. placebo (80.3% vs. 69.8%; HR = 0.66; 95% CI, 0.47-0.93).
Researchers also conducted an indirect comparison with these data and bisphosphonate meta-analysis data. Data from the Early Breast Cancer Trialists’ Group showed a 3% gain in recurrence benefit at 10 years with bisphosphonates.
“I believe it’s fair to say that adjuvant denosumab does at least as much as adjuvant bisphosphates do,” Gnant said. “I believe that we should offer this treatment to postmenopausal breast cancer patients on aromatase inhibitors.” – by Alexandra Todak
Disclosure: The study was funded by Amgen. Gnant reports research grants unrelated to this study from GlaxoSmithKline, Novartis, Pfizer, Roche, Sanofi and Smith Medical.