Zoledronic Acid Did Not Prevent Bone Metastases in High-Risk Prostate Cancer

The use of zoledronic acid (Zometa) had no effect on the prevention of bone metastases in patients with high-risk prostate cancer, according to the first results of the Zometa European Study, or ZEUS, presented at the European Association of Urology 28th Annual Congress in Milan, Italy.

Ball-and-stick model of zoledronic acid

“There were no differences in the incidence of bone metastasis,” said Manfred Wirth, MD, professor of urology at the Dresden University of Technology, in Dresden, Germany.

Wirth declared the trial to be “negative” for failing to meet its primary endpoint of a percentage difference in patients who developed bone metastases based on local image evaluation.

The ZEUS trial included 1,433 men with high-risk prostate cancer defined as a PSA score at diagnosis of 20 ng/dL or higher, a Gleason score of 8 to 10, or lymph node positivity. Patients were randomly assigned to treatment with 4 mg of zoledronic acid every 3 months for 48 months (n = 716) or to the control arm (n = 717).

Patients in the zoledronic acid arm were followed for a median of 4.7 years, and patients in the control arm for 4.8 years. No difference in the rate of bone metastases was found between the two groups at the end of follow-up (13.7% for zoledronic acid vs 13% for control).

More adverse events were reported among patients in the zoledronic acid arm compared with the control arm. In addition, more patients in the zoledronic acid arm withdrew due to adverse events, including fever and flu-like symptoms, joint pain, and osteonecrosis of the jaw.

The researchers also conducted a subgroup analysis that looked at the effect of prior local curative treatment.

“Patients with no prior local curative treatment had a significantly higher metastases rate than those receiving prior curative treatment,” said Wirth. “This is a very interesting result of the trial that seems to show that local curative treatment really is of benefit for those patients not to develop metastases.”

Among patients in the zoledronic acid arm, 11.2% with prior treatment developed metastases vs 16.9% of patients with no prior treatment. In the control arm, 9.9% of patients developed bone metastases compared with 16.7% with no prior treatment.

The study showed no difference in overall survival between the two groups.

A second subgroup analysis identified a regional variation of patients who developed bone metastases. Using Germany, which is where the majority of patients were enrolled, as a reference, data indicated that patients in Sweden, the Netherlands, and Norway had a significantly increased risk for metastasis. In contrast, patients in Italy had a reduced risk.