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Updated: Jul 12, 2026
Single-Port Robotic-assisted Transaxillary Breast-conserving Surgery: A Prospective, Single-arm, Non-randomized Phase IIa Clinical Trial
Published on: August 19, 2025
Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer-related
Allan Lipton1, Guenther G Steger, Jazmin Figueroa
1Penn State Milton S. Hershey Medical Center, Hershey, PA 17033-0850, USA. alipton@psu.edu
Purpose:
Denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor-kappaB ligand, suppresses bone resorption. In this study, we evaluated the efficacy and safety of five dosing regimens of denosumab in patients with breast cancer-related bone metastases not previously treated with intravenous bisphosphonates (IV BPs).
Patients And Methods:
Eligible women (n = 255) with breast cancer-related bone metastases were stratified by type of antineoplastic therapy received and randomly assigned to one of six cohorts (five denosumab cohorts [blinded to dose and frequency]; one open-label IV BP cohort). Denosumab was administered subcutaneously every 4 weeks (30, 120, or 180 mg) or every 12 weeks (60 or 180 mg). The primary end point was percentage of change in the bone turnover marker urine N-telopeptide corrected for urine creatinine (uNTx/Cr) from baseline to study week 13. The percentage of patients achieving more than 65% uNTx/Cr reduction, time to more than 65% uNTx/Cr reduction, patients experiencing one or more on-study skeletal-related events (SRE), and safety were also evaluated.
Results:
At study week 13, the median percent reduction in uNTx/Cr was 71% for the pooled denosumab groups and 79% for the IV BP group. Overall, 74% of denosumab-treated patients (157 of 211) achieved a more than 65% reduction in uNTx/Cr compared with 63% of bisphosphonate-treated patients (27 of 43). On-study SREs were experienced by 9% of denosumab-treated patients (20 of 211) versus 16% of bisphosphonate-treated patients (seven of 43). No serious or fatal adverse events related to denosumab occurred.
Conclusion:
Subcutaneous denosumab may be similar to IV BPs in suppressing bone turnover and reducing SRE risk. The safety profile was consistent with an advanced breast cancer population receiving systemic therapy.
Insights
Denosumab effectively suppresses bone resorption in breast cancer patients with bone metastases, showing comparable efficacy to intravenous bisphosphonates in reducing bone turnover and skeletal-related events. The drug demonstrated a favorable safety profile in this patient population.
Area of Science:
- Oncology
- Pharmacology
- Bone Metabolism
Background:
- Bone metastases are a common complication in advanced breast cancer.
- Bone resorption is a key process in the development of bone metastases.
- Intravenous bisphosphonates (IV BPs) are standard treatment for bone metastases, but alternatives are being explored.
Purpose of the Study:
- To evaluate the efficacy and safety of denosumab, a monoclonal antibody targeting receptor activator of nuclear factor-kappaB ligand (RANKL), in patients with breast cancer-related bone metastases.
- To compare five different subcutaneous denosumab dosing regimens against a standard IV bisphosphonate treatment.
- To assess denosumab's impact on bone turnover markers and skeletal-related events (SREs).
Main Methods:
- A randomized study involving 255 women with breast cancer and bone metastases.
- Patients received subcutaneous denosumab (various doses/frequencies) or intravenous bisphosphonates.
- Primary endpoint: change in urine N-telopeptide corrected for urine creatinine (uNTx/Cr) at week 13.
- Secondary endpoints included SREs and safety assessments.
Main Results:
- Denosumab treatment led to a median 71% reduction in uNTx/Cr, comparable to IV BPs (79%).
- 74% of denosumab patients achieved >65% uNTx/Cr reduction versus 63% for IV BPs.
- Skeletal-related events occurred in 9% of denosumab patients vs. 16% of IV BP patients.
- No serious or fatal adverse events were attributed to denosumab.
Conclusions:
- Subcutaneous denosumab demonstrates comparable efficacy to IV bisphosphonates in suppressing bone turnover and reducing SRE risk.
- Denosumab presents a potentially effective and safe treatment option for breast cancer patients with bone metastases.
- The safety profile of denosumab is consistent with that expected in advanced breast cancer patients receiving systemic therapy.
