We have long known that Zoledronic Acid (Zometa) decreases a man’s risk of developing skeletal-related events (SREs) in men with castration-resistant advanced prostate cancer (CRPC) and bone metastases.

In a phase III study that evaluated efficacy and safety of earlier treatment with Zometa in men with advanced prostate cancer which is still castration-sensitive found that it did not lower the risk of developing SREs or extend life.

This trial (CALGB 90202) was a randomized, double-blinded, placebo-controlled phase III trial in men with castration-sensitive prostate cancer and bone metastases who had initiated androgen deprivation therapy within six months of study entry. The men were randomized 1:1 in blinded manner to receive Zometa (4 mg intravenously every 4 weeks) or placebo. Once the men progressed and became castrate resistant (CRPC) they crossed over to receive Zometa.

The primary endpoint of the trial was time to the development of the first SRE. With 470 SRE events the study was discontinued prematurely after the corporate supporter withdrew study drug supply.

Anaylisis of the collected data between June 2004 and April 2012 included 645 men who were randomly assigned to Zometa or placebo. Median time to first SRE was 32.5 months in the Zometa group and 29.8 months in the placebo group (hazard ratio (HR) 0.96

[0.76-1.22]; stratified log-rank P=0.74).

A total of 271 deaths were observed; median follow-up time for surviving patients was 24.4 months). Overall survival was similar between groups (HR= 0.89 [0.70-1.14]; stratified P=0.34). Rates of grade 3 or higher adverse events were similar between groups.

The data concluded that men with castration-sensitive prostate cancer and bone metastases, early treatment with zoledronic acid was not associated with lower risk for SREs or death. Early termination limited statistical power of the study.

Bottom Line: Starting Zometa while you remain hormone sensitive brings no additional benefits but exposes you to potentially developing earlier side effects. Do not start Zometa until you become castrate resistant.

J Clin Oncol 31, 2013 (suppl 6; abstr 27): Matthew Raymond Smith, Susan Halabi, Charles J. Ryan, Walter Michael Stadler, Arif Hussain, Nicholas J. Vogelzang, Ralph J. Hauke, Ben L. Sanford, Eric Jay Small, Alliance; Massachusetts General Hospital Cancer Center, Boston, MA; Alliance Statistical and Data Center/Duke University Medical Center, Durham, NC; USCF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; University of Chicago, Chicago, IL; University of Maryland, Baltimore, MD; Comprehensive Cancer Centers of Nevada, Las Vegas, NV; University of Nebraska Medical Center, Omaha, NE; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA

Clinical trial information: NCT00079001.

Joel T. Nowak, M.A., M.S.W.