Stay Up to Date
Breaking News,
Updates, & More
Click Here to
Subscribe

To Protect Bone, Denosumab Outperforms Zoledronic Acid in Breast Cancer Patients

TOP - April 2010 Vol 3, No 2 published on June 10, 2010 in Breast Cancer

For the prevention of skeletal-related events (SREs) in breast cancer patients with bone metastasis, denosumab proved superior to zoledronic acid (ZA) in a head-to-head randomized comparison conducted in 2048 women.

"Denosumab prevented more events, was better tolerated, and, as a subcutaneous [SC] injection, was more convenient for patients in this randomized double- blind trial against what has been the standard of care for treating bone metastasis," said Alison Stopeck, MD, of the University of Arizona Cancer Center, Tucson, who described the study at a press briefing.

She told reporters that should denosumab become US Food and Drug Administration (FDA)-approved, she will incorporate the drug "quickly" into her care of patients with bone metastases, "because subcutaneous administration is easy, you don't need to monitor creatinine, and it is less toxic, assuming the price is not exorbitant."

Denosumab works by inhibiting RANK ligand, which regulates osteoclast activity and function. It is not yet FDA-approved for use in metastatic breast cancer.

Patients with bone metastases not previously treated with intravenous (IV) bisphosphonates were randomized to treatment with SC denosumab 120 mg every 4 weeks and IV placebo, or SC placebo and IV ZA 4 mg every 4 weeks. Patients also received supplemental calcium and vitamin D.

During the 34-month study, 36.5% of patients treated with ZA developed SREs compared with 30.7% receiving denosumab, for a 6% absolute reduction in risk and a 16% relative risk reduction, Stopek announced.

The study's primary end point, time to first on-study SRE (pathologic fracture, radiation or surgery to bone, or spinal cord compression), was significantly shorter with ZA, at a median of 26.5 months, whereas half the denosumab-treated group has not yet experienced an SRE (ie, the end point has not been reached), Stopek reported.

"We also assessed whether staying on denosumab was beneficial, since patients who have an SRE are at risk for a second one," she said. Again, the benefit of denosumab was clear, as time to first-andsubsequent on-study SRE was reduced by 23%, over ZA. At 30 months, 608 events occurred with ZA compared with just 474 events with denosumab, a highly significant difference.

"Another encouraging observation was that the curves continue to separate," she added. "We expect the data to continue to strengthen as patients are on the drug longer."

Denosumab was also more protective against hypercalcemia of malignancy, and was superior in an analysis of skeletal morbidity rate.

"Most importantly for patients," she said, denosumab was associated with a delay in the onset of moderate-to-severe pain, from 64 days with ZA to 88 days. "What makes bone metastases so brutal is the pain, and patients on denosumab took longer to develop moderate-tosevere pain," she reported.

Adverse events were similar, although ZA was associated with higher incidence of acute-phase reactions (27.3% vs 10.4%). There was more renal toxicity with ZA but more hypercalcemia with denosumab. The occurrence of osteo necrosis of the jaw (ONJ) was rare and was not significantly different between the groups, occurring in 14 patients (1.4%) with ZA and 20 (2.0%) with denosumab. Importantly, 80% of subjects developing ONJ had risk factors for the condition, including dental extraction, poor dental hygiene, or dental appliances.

Theresa Guise, MD, professor of medicine and Jerry W. and Peg S. Throg martin professor of oncology at Indiana University School of Medicine, commented as moderator of the press briefing: "This study is very important. It shows that by inhibiting bone resorption in different ways we can get improved effects on preventing SREs." 

Related Items
Olaparib Extends Disease-Free Survival in Patients with Early-Stage Breast Cancer and BRCA Mutation
William King
TOP - November 2021 Vol 14, No 7 published on November 10, 2021 in Breast Cancer
Tucatinib plus Trastuzumab and Capecitabine Triplet Maintains Survival Benefit in HER2-Positive Metastatic Breast Cancer: Updated Results from HER2CLIMB Trial
Charlie Dawson
TOP - September 2021 Vol 14, No 5 published on September 7, 2021 in Breast Cancer
Cryoablation Appears Safe and Effective in Low-Risk, Early-Stage Breast Cancer
William Ackerman
TOP - July 2021 Vol 14, No 4 published on July 20, 2021 in Breast Cancer
Pembrolizumab plus Chemotherapy Improves Progression-Free Survival in Metastatic TNBC
Patricia Stewart
TOP - May 2021 Vol 14, No 3 published on May 14, 2021 in Breast Cancer
Abemaciclib plus Endocrine Therapy Offers Invasive Disease–Free Survival Benefit in Patients with High-Risk, HR-Positive, Early-Stage Breast Cancer
Patricia Stewart
TOP - May 2021 Vol 14, No 3 published on May 14, 2021 in Breast Cancer
Breast Cancer Year in Review Introduction
2020 Year in Review - Breast Cancer published on January 24, 2021 in Breast Cancer
Retrospective Analysis Provides Insight into Treatment-Emergent Neutropenia Among Patients with Metastatic Breast Cancer Treated with Ribociclib or Palbociclib
2020 Year in Review - Breast Cancer published on January 24, 2021 in Breast Cancer
Concurrent Use of Medications with Potential Drug–Drug Interactions: Real-World Analysis of Patients Treated with CDK4/6 Inhibitors
2020 Year in Review - Breast Cancer published on January 24, 2021 in Breast Cancer
Abemaciclib plus Fulvestrant Provides Statistically Significant Benefit as First- and Second-Line Therapy for Hormone Receptor–Positive, HER2-Negative Advanced Breast Cancer
2020 Year in Review - Breast Cancer published on January 24, 2021 in Breast Cancer
Preliminary Results from a Phase 2 Trial of Fulvestrant/Palbociclib as First-Line Therapy in Postmenopausal Women with Hormone Receptor–Positive, HER2-Negative Endocrine-Sensitive Advanced Breast Cancer
2020 Year in Review - Breast Cancer published on January 24, 2021 in Breast Cancer
Last modified: July 22, 2021