Denosumab versus zoledronic acid in patients with bone metastases from solid tumors other than breast and prostate cancers or multiple myeloma: A number needed to treat (NNT) analysis.

Abstract

9115 Background: Bone metastases (mets) are a common complication of advanced cancer. In a study of patients (pts) with metastatic bone disease, denosumab was non-inferior to zoledronic acid (ZA) for time to 1st skeletal-related event (SRE; HR 0.84 [95% CI 0.71, 0.98]; P = 0.0007), with a trend toward superiority (P = 0.06). This analysis describes the NNT with denosumab versus ZA to prevent one additional SRE. Methods: Pts with bone mets from solid tumors (other than breast or prostate) or bone lesions due to MM were randomized in a double-blind, phase III trial to receive SC denosumab 120 mg or IV ZA 4 mg every 4 weeks. The primary endpoint was time to 1st SRE (non-inferiority) defined as a composite endpoint of fracture, radiotherapy to bone, surgery to bone, or spinal cord compression. Key secondary endpoints were time to 1st on-study SRE (superiority) and time to 1st and subsequent SREs (superiority, multiple event analysis). The NNT for denosumab compared with ZA was calculated for 1st SRE and 1st and subsequent SREs. NNT data are reported in pt-years to describe treatment benefit regardless of treatment duration. Results: Overall, 1776 pts enrolled: 886 denosumab and 890 ZA. A 1st on-study SRE was experienced by 278 denosumab pts and 323 ZA pts. Fewer 1st or subsequent SREs were experienced by pts in the denosumab arm vs the ZA arm, reflecting a risk reduction of 10% vs ZA (RR 0.90 [95% CI 0.77, 1.04]; P = 0.14). Compared with ZA, the NNT analysis showed that treatment of 9.9 pts with denosumab would prevent one additional 1st SRE per year, and treatment of 10.4 pts with denosumab would prevent one additional 1st or subsequent SRE per year. In the subgroup of patients with bone mets from solid tumors, denosumab pts experienced fewer SREs than ZA pts (RR 0.85 [95% CI 0.72, 1.00]; P < 0.05]). Compared with ZA, the NNT analysis showed that treatment of 6.5 pts with denosumab would prevent one additional 1st or subsequent SRE per year. Conclusions: The low NNT for each SRE prevented shows the therapeutic efficacy for denosumab in these pts compared with ZA. Denosumab is a new treatment option for the prevention of SREs in advanced cancer pts with metastatic bone disease.