Denosumab improves DFS, bone-related outcomes in breast cancer subtype

Michael Gnant

Adjuvant denosumab may improve DFS and bone-related outcomes among postmenopausal women with early-stage, hormone receptor-positive breast cancer receiving adjuvant aromatase inhibitor therapy, according to findings from the ABCSG-18 trial presented at the ASCO Annual Meeting.

“Adjuvant aromatase inhibitors are [the] standard of care for postmenopausal women with HR-positive, early-stage breast cancer, but [the agents] cause osteoporosis and fractures,” the authors wrote. “ABCSG-18 showed previously that adjuvant denosumab significantly reduces clinical fractures. Here, we present the impact of adjuvant denosumab on disease-free survival.”

Michael Gnant, MD, of the Comprehensive Cancer Center at the Medical University of Vienna, and colleagues enrolled 3,420 patients from 58 centers in this prospective, double-blind, placebo-controlled, phase 3 trial. Patients were randomly assigned 1:1 to receive subcutaneous 60 mg denosumab (n = 1,711) or placebo (n = 1,709) every 6 months during treatment with aromatase inhibitors. DFS served as the secondary endpoint and included “relevant subgroup and sensitivity analyses (accounting for cross-over either by censoring or by using a rank preserving structural failure time model),” according to the study authors.

Median follow-up was 72 months, at which time 240 and 287 events had occurred in the denosumab and placebo groups, respectively. DFS was 89.2% (95% CI, 87.6%-90.7%) at 5 years and 80.6% (95% CI, 78.1%-83.1%) at 8 years in the denosumab arm. In the placebo arm, DFS was 87.3% (95% CI, 85.7%-89%) at 5 years and 77.5% (95% CI, 74.8%-80.2%) at 8 years.

DFS “significantly improved” among patients in the denosumab arm, according to the authors. In addition, sensitivity analyses demonstrated comparable results.

The authors did not report any cases of osteonecrosis of the jaw, despite what they call “proactive adjudication of potential cases by an independent expert panel.” One potentially unusual femur fracture was observed in the denosumab arm.

These results, and “the previously reported dramatic reduction of fractures,” indicate that adjuvant denosumab 60 mg given subcutaneously every 6 months should be offered to postmenopausal women with HR-positive breast cancer who are receiving treatment with aromatase inhibitors, according to the authors. – by Julia Ernst, MS

Reference:

Gnant M, et al. Abstract 500. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.

Disclosures: Gnant is employed by Sandoz. He also reports a consultant/advisory role with Accelsiors; honoraria from Amgen, AstraZeneca, Celgene, Eli Lilly, NanoString Technologies, Novartis and Roche; research funding through his institution from AstraZeneca, Novartis, Pfizer and Roche; and travel, accommodations and expenses from Amgen, AstraZeneca, Celgene, Eli Lilly, Ipsen, Medtronic, Novartis and Pfizer.