Related ACE Reports
- Author Verified
- Published: Mar 2011
- ACE Report #5244
Denosumab noninferior to zoledronic acid in the treatment of bone metastasis
Study Type: Therapy
OE Level of Evidence: 1
Journal Level of Evidence: N/A
|Sponsor:||Amgen, Thousand Oaks, CA.|
Why was this study needed now?
In patients with bone metastases or myeloma, skeletal-related events (SREs) (i.e. fracture, need for surgery, spinal compression and hypercalcemia) occur as a result of excessive bone degredation by osteoclasts. Previous studies have found that zoledronic acid, a bisphosphonate administered intravenously, is effective in increasing the time until an SRE, however, it is also associated with renal failure, acute phase reactions (a flu-like condition), and osteonecrosis of the jaw. A new drug, denosumab, is thought to reduce osteoclast activity by inhibiting the receptor activator of nuclear factor kappa-B ligand (RANKL) without inducing acute-phase reactions or renal impairment. Therefore, this trial was needed to compare the efficacy and safety of denosumab with the current treatment option, zoledronic acid.
What was the principal research question?
Is denosumab comparable to zoledronic acid in terms of efficacy and safety in patients with bone metastasis, when assessed at 34 months?
|Population:||1,779 patients, over the age of 18 years, with solid tumours (except breast and prostate) or myeloma, as well as at least 1 bone metastasis or osteolytic lesion as confirmed by radiographic imaging.|
|Intervention:||Denosumab group (n=886, 190 available for final follow up): Patients in this group received subcutaneous injections of denosumab 120 mg and an intravenous (IV) infusion of placebo every 4 weeks. Supplementation of calcium (500 mg or more) and vitamin D (400 U or more) was recommended to patients, and specific anticancer and other concomitant medications were allowed|
|Comparison:||Zoledronic acid group (n=890, 178 available for final follow up): Patients in this group received an intravenous infusion (lasting a minimum of 15 minutes) of zoledronic acid 4 mg (Zometa, Novartis Pharmaceuticals, East Hanover, NJ) (dose adjusted in the case of renal impairment), and a subcutaneous injection of placebo every 4 weeks. Supplementation of calcium (500 mg or more) and vitamin D (400 U or more) was recommended to patients, and specific anticancer and other concomitant medications were allowed.|
|Outcomes:||The primary efficacy outcome was skeletal-related events (SRE). Only when non-inferiority was established were secondary efficacy outcomes assessed. These included time to first on-study SRE and time to first-and-subsequent SRE (defined as an SRE occurring 21 or more days following the first SRE). Safety outcomes included treatment-emergent adverse events (AEs) and serious adverse events (SAEs), changes in laboratory values and the incidence of both binding and neutralizing antidenosumab antibodies.|
|Methods:||RCT: Multi Center: Double-blind (patients & assessors)|
What were the important findings?
What should I remember most?
How will this affect the care of my patients?
The authors responsible for this critical appraisal and ACE Report indicate no potential conflicts of interest relating to the content in the original publication.