CHICAGO—Denosumab delayed or prevented more skeletal-related adverse events than zoledronic acid in men with hormone-refractory prostate cancer and bone metastases.
The superior efficacy of denosumab on this end point along with its ease of administration—subcutaneous rather than intravenous—gives it an edge over zoledronic acid, said Karim Fizazi, MD, PhD, lead investigator of a study comparing the two treatments.
Earlier this year, denosumab was granted US Food and Drug Administration approval for the treatment of postmenopausal women who have a high risk for osteoporotic fractures, including those with a history of fracture or multiple risk factors for fracture, or those who have failed or are intolerant to other osteoporosis therapy.
Denosumab specifically targets RANK ligand, a central mediator of the “vicious cycle” of bone destruction in metastatic cancer, said Fizazi, head, Department of Medical Oncology, Institut Gustave-Roussy, Villejuif, France.
In the trial, 1901 patients with hormone-refractory (castration-resistant) prostate cancer with bone metastases were randomized to denosumab given subcutaneously every 4 weeks, or zoledronic acid given intravenously every 4 weeks. Eighty percent of patients in each study arm discontinued therapy, mainly due to death or cancer progression, and rarely because of side effects, he said.
The time to a first skeletal-related event—the primary efficacy end point—was delayed by 18% with denosumab compared with zoledronic acid. The median time to first on-study skeletal-related event was 20.7 months for denosumab compared with 17.1 months for zoledronic acid.
The time to all on-study skeletal-related events was also delayed by 18% in patients assigned to denosumab versus those on zoledronic acid.
There was no significant difference in cancer progression and no significant
difference in overall survival
between the two treatment arms.
Some 97% of patients in each group had adverse events, most of which were related to the underlying cancer:
- The rates of infectious adverse events were 42.6% in the denosumab group and 39.7% in the zoledronic acid group.
- Infectious serious adverse events occurred in 13.8% of patients assigned to denosumab compared with 11.4% of those assigned to zoledronic acid.
- Acute-phase reactions occurred in about twice as many patients assigned to zoledronic acid versus denosumab (17.8% vs 8.4%).
- Hypocalcemia was more common in the denosumab arm than in the zoledronic acid arm (12.8% vs 5.8%).
- There were 22 cases of osteonecrosis of the jaw in the denosumab group (2.3%) compared with 12 in the zoledronic acid group (1.3%).
About 80% of patients in each treatment group who experienced osteonecrosis of the jaw had risk factors for it at baseline, such as tooth extraction, dental appliances,
or poor oral hygiene.
In addition to its subcutaneous route of delivery instead of intravenous infusion, Fizazi said that no renal monitoring or dose adjustment is needed with denosumab as opposed to zoledronic acid, nor is there a need to manage acute-phase reactions. To date, more than 11,000 patients have been exposed to denosumab in clinical trials of patients with cancer or bone loss.