Clinical Summary:

• Design/Population: The phase 3 SAKK 96/12 REDUSE noninferiority trial randomized patients with bone metastases from breast cancer or castration-resistant prostate cancer to receive denosumab every 4 weeks or a de-escalated schedule of every 12 weeks after a 3-month induction period.
• Key Outcomes: Every-12-week denosumab was noninferior to standard dosing for time to first symptomatic skeletal event, with both groups achieving a median time to event of 56 months. The de-escalated schedule reduced rates of hypercalcemia by 30%, osteonecrosis of the jaw by 25%, and medication costs by 53%.
• Clinical Relevance: These findings support less frequent denosumab administration as an effective strategy to maintain skeletal protection while reducing toxicity, treatment burden, and healthcare costs.

Roger von Moos, MD, Kantonspital Graubünden, Chur, Switzerland, discusses results from the phase 3 SAKK 96/12 REDUSE trial evaluating whether denosumab dosing could be safely reduced in patients with metastatic bone disease. The study compared standard every-4-week administration with a de-escalated schedule of every 12 weeks following an induction phase.

Results demonstrated that less frequent dosing maintained protection against symptomatic skeletal events while reducing clinically important toxicities, including hypercalcemia and osteonecrosis of the jaw. These findings suggest that every-12-week denosumab may provide comparable efficacy with improved tolerability and substantially lower treatment costs.

Dr von Moos presented these results at the 2026 ASCO Annual Meeting in Chicago, Illinois.

Transcript: 

My name is Roger von Moos. I’m here on behalf of the Swiss Cancer Institute and our more than 40 investigators across Switzerland. We studied the prevention of skeletal events in patients with metastatic breast cancer or castration-resistant prostate cancer with bone metastases.

What we know up to now is that the standard of care is to give denosumab, a RANK ligand antibody, every 4 weeks, this has been the standard approach. Based on preclinical data, we were convinced that the treatment could be given less frequently. That’s why we initiated a phase 3 noninferiority trial with 1,380 patients randomized 1:1. In one arm, patients received the standard schedule of denosumab every 4weeks. In the other arm, patients received an induction phase over 3 months, for a total of 4 doses, and then continued treatment every 12 weeks. The primary end point was time to first symptomatic skeletal event. This is slightly different from the pivotal trials, where skeletal-related events were the primary end point. We did not capture asymptomatic fractures; we only captured symptomatic skeletal events, meaning that the endpoint was triggered by symptoms.

We found that the 12-week arm was noninferior to the 4-week arm, with a hazard ratio of 1.02 and an upper confidence interval boundary of 1.197, which remained below the predefined noninferiority margin of 1.20. In both groups, the median time to first symptomatic skeletal event was 56 months.

As a secondary end point, we evaluated time to first and subsequent skeletal events, and this end point also demonstrated noninferiority. In fact, the results were essentially identical between the 2 treatment schedules. Further down the road, we were of course interested in toxicity.

In the 12-week arm, we observed a relative reduction of approximately 30% in hypercalcemia and a 25% reduction in osteonecrosis of the jaw. As another important end point, we found that medication costs could be reduced by 53%.

In summary, the REDUSE trial, SAKK 96/12, demonstrated clear noninferiority of the 12-week schedule compared with the standard 4-week schedule, with reduced toxicity in terms of hypercalcemia and osteonecrosis of the jaw, as well as substantially lower treatment costs. For these reasons, we believe that the 12-week schedule should become the new standard of care for these patients.

Source: 

Von Moos RAF, Müller A, Hayoz S, et al. Prevalence of symptomatic skeletal events (SSE) with reduced denosumab (Dmab) dose density (every 12 weeks versus every 4 weeks): A randomized phase III non-inferiority trial SAKK 96/12 REDUSE. Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. Abstract 1004.