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Addition of abiraterone to HT could eliminate tumors in some men with high-risk prostate cancer
Mary-Ellen Taplin
The addition of abiraterone during 6 months of hormonal therapy prior to surgery eliminated or nearly eliminated tumors in one-third of men with localized high-risk prostate cancer, according to study results.
Abiraterone (Zytiga, Janssen Biotech) traditionally is used to treat advanced prostate cancer. This randomized phase 2 trial was the first to explore its use in early-stage treatment, the researchers said.
“Abiraterone works by blocking production of the male hormone testosterone and related metabolites that often fuel cancer growth,” Mary-Ellen Taplin, MD, associate professor of medicine at Harvard Medical School and Dana-Farber Cancer Institute, said in a press release. “The addition of abiraterone to traditional hormonal therapy, which restricts testosterone production in a different way, further shuts down the body’s ability to produce the hormones that cancer cells need for growth.”
Taplin and colleagues evaluated the effects of adding abiraterone to leuprolide prior to surgical removal of the prostate.
The researchers divided patients into two groups. Group A consisted of 27 men who received leuprolide for 12 weeks, followed by leuprolide plus abiraterone for another 12 weeks. Group B consisted of 29 men who received both leuprolide and abiraterone for the entire 24-week period. All patients underwent prostatectomy after 24 weeks of therapy, and researchers evaluated tissue for evidence of cancer.
Thirty-four percent of men assigned to 24 weeks of abiraterone therapy had either complete elimination or nearly complete elimination of cancer, compared with 15% of men assigned to 12 weeks of abiraterone therapy.
The treatment was well tolerated by both groups, the researchers said. Grade-3 adverse events included elevated aspartate and alanine aminotransferase (9%) and hypokalemia (5%). No grade-4 adverse events were reported.
“Historically, pathologic complete response rate with any type of standard hormone therapy is 5% or less, so these rates are very impressive given the high-risk features of these patients,” Taplin said during a press conference.
The findings suggest that this combination therapy could improve outcomes for a substantial number of men, researchers said.
“The rates of complete response and near-complete response in the prostate were very high in these high-risk prostate cancer patients,” Taplin said during the press conference. “The long-term significance of obtaining a complete response like this needs to be validated in larger studies.”
Reference:
- Taplin ME. Abstract #4521.
Disclosure:
- Dr. Taplin has served as a consultant and adviser to, and received honoraria and research funding from, Johnson & Johnson.
Perspective
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Abiraterone acetate (AA) is a potent cyp17 inhibitor that inhibits both adrenal and intratumoral androgen synthesis. In April 2011, AA was approved by the FDA after demonstrating a significant OS benefit in men with metastatic castration-resistant prostate cancer who had previously received cytotoxic therapy with docetaxel. Since AA is beneficial in the most advanced metastatic stages of prostate cancer, it stands to reason that using it in earlier stages of the disease might be of benefit as well. Toward that end, Dr. Taplin and her collaborators have looked at AA in combination with prednisone and leuprolide acetate (LHRHa) in men with locally advanced, high-risk prostate cancer who are planning to undergo prostatectomy. Six months of AA plus prednisone plus LHRHa resulted in a pathologic complete response (pCR)/near pCR rate of 34% (vs. a 5% pCR with LHRHa alone in historical controls). Although it is not yet known whether an increased rate of pCR will equate with an OS benefit in this pre-surgical population, this study opens the door to further exploration of neoadjuvant therapy in prostate cancer using novel androgen-receptor targeted treatments and offers an invaluable opportunity to explore the mechanisms of response and resistance to these interventions in available prostate tissue specimens.
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Abiraterone acetate did not appear to be associated with any unexpected or difficult toxicities in this group of patients. There were no new “safety signals” seen, so I think we can continue to be confident that abiraterone is a well-tolerated, safe drug even to give to patients in the period preceding radical prostatectomy. The other important finding was that, in those individuals who received abiraterone acetate and androgen deprivation [therapy], there seemed to be more complete response of the tumor in the prostate. The complete pathologic response or near-complete response was 34% in the abiraterone acetate plus androgen deprivation [arm], while it was 15% in the patients receiving androgen deprivation alone, so it was more than a doubling of complete or near-complete response rate by the addition of abiraterone to standard androgen deprivation. Cautions in the interpretation of this trial must reflect on the fact that it is a relatively small trial … but I think we can conclude that abiraterone in this setting is safe, and the signal based on this trial is that there does appear to be more substantial anti-tumor effect in this neoadjuvant period than by the combination of abiraterone and androgen deprivation compared with standard androgen deprivation alone. We also must continue to reflect on the difficulty that exists in showing that neoadjuvant therapy in men with prostate cancer prior to prostatectomy influences outcome. So I think this trial sets the stage for further study, and importantly, demonstrates the safety of abiraterone, but [it] does not provide a body of data on which practice should be changed.