Nick Mulcahy

May 16, 2012

May 16, 2012 — The targeted therapy abiraterone (Zytiga; Janssen), which is approved for the treatment of advanced prostate cancer, may also be a boon to men with localized high-risk prostate cancer.

A randomized phase II study shows that 6 months of neoadjuvant abiraterone eliminated or nearly eliminated cancer in one-third of the men at that juncture, reported study lead author Mary-Ellen Taplin, MD, of the Dana-Farber Cancer Institute in Boston Massachusetts.

She spoke at a press briefing that precedes the annual meeting of the American Society of Clinical Oncology in Chicago, Illinois, where the study will be presented in full in June.

Specifically, 34% of men treated with abiraterone for 6 months had either pathological complete response(pCR; 3/29) or near pCR (7/29).

This was superior to the results in men treated with abiraterone for only 3 months. Only 15% of these men had either pCR (1/27) or near pCR (3/27).

All of the men in the study also received standard hormone therapy for 6 months and underwent prostatectomy after completing drug therapies.

The difference in response between the 2 study groups was not statistically significant, but the response rates among the men who received arbiraterone for six months are unprecedented, said Dr Taplin.

“One third of the patients have minimal or no tumor when go to the OR,” told Medscape Medical News in an interview after the press conference. “That’s never been seen before.”

That's never been seen before

Historically, pCR rates have been 5% or less with traditional hormone therapy when it has been employed in the neoadjuvant setting with these patients, Dr Taplin explained. And those rates were generally established in studies of men who had localized disease of lesser risk than the patients in the current study, she said.

In the new study, the participants had either a Gleason score of ≥ 7 (4+3), stage T3 disease, a PSA score of ≥ 20 ng/mL or a PSA velocity > 2 ng/mL/year. The median age was 58 years and 35% had nodal involvement.

The need for an effective additional therapy for men with such high risk disease is great, she suggested.

Localized high-risk disease, which accounts for about 15% of all prostate cancer, is infrequently cured with prostatectomy, and almost all men will eventually die of the disease, said Dr Taplin. To date, other neoadjuvant systemic therapy has not improved outcomes in prostate cancer.

That could change with abiraterone, suggested a cancer expert not involved with the study.

“This is an exciting new step forward” summarized Nicholas Vogelzang, MD chair of the ASCO Communications Committee, who moderated the press conference. He said that the new study was likely the first to show that neoadjuvant therapy “can make prostate cancer disappear in the prostate gland in a reproducible number of patients.”

The study results are very promising, he suggested. “When you get complete disappearance in the primary disease, the outcomes are much better,” said Dr. Vogelzang, referring to survival improvements seen in breast, bladder and other cancers when treated neoadjuvantly.

A randomized phase 3 trial that validates the current study findings is needed next, said Dr Taplin. However, she told Medscape Medical News that no such trial is currently planned.

Adverse Events; Other Studies

Arbiraterone was “well tolerated,” report the authors. Grade 3 adverse events included elevated AST/ALT (5/58; 9%) and hypokalemia (3/58; 5%). No grade 4 mineralocorticoid-related adverse events were observed. When receiving arbiraterone, men also received prednisone 5mg four times a day to mitigate mechanism-related side effects of abiraterone. No new “safety signals” were seen with the drug in the new study.

Abiraterone is a logical choice for treating men with earlier stage yet high risk disease because it has been shown to lower serum testosterone and DHT to < 1 ng/dL and to improve survival in advanced prostate cancer, write Dr Taplin and her coauthors in their abstract. They will further report their findings from this study about abiraterone’s effect on serum testosterone and DHT at the ASCO meeting.

Dr Taplin explained that the combination of abiraterone and traditional hormonal therapy makes good sense. “Prostate cancer cells rely on androgen to grow,” she said.

Abiraterone blocks androgen biosynthesis. Traditional hormonal therapy, which in this study was leuprolide acetate (Lupron),restricts testosterone production in a different and complimentary way.

The approach of intensive androgen deprivation is also being tested in a number of other clinical trials, Dr Taplin said. Another phase II study is investigating the novel androgen signaling inhibitor, MDV3100, in the neoadjuvant setting for high risk prostate cancer. And a clinical trial program investigating the addition of the investigational drug ARN509 to abiraterone and hormone therapy is being developed.

The study was funded by Cougar Biotechnology, Johnson & Johnson, and the Prostate Cancer Foundation.

Mary-Ellen Taplin, MD, reports being a consultant or advisor; receiving honoraria and research funding with Johnson & Johnson. Other authors are employees of the company. Dr Vogelzang reports multiple financial ties to industry including those with prostate cancer interests.

2012 Annual Meeting of the American Society of Clinical Oncology: Abstract 4521. To be presented June 2, 2012.

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