Neoadjuvant Zytiga Helps Eliminate Some Patients' Prostate Tumors

Mary-Ellen Taplin, MD

Combined neoadjuvant treatment with abiraterone acetate (Zytiga) plus standard hormonal therapy before prostatectomy eradicated or nearly eradicated tumors in 34% of patients with localized high-risk prostate cancer, according to the results of a phase II randomized trial. The study will be presented at the upcoming 2012 ASCO Annual Meeting in Chicago, Illinois.

“Patients who present with high-risk local disease have very low cure rates with local therapies and, over time, generally succumb to prostate cancer,” said Mary-Ellen Taplin, MD, associate professor of Medicine at Harvard Medical School and the Dana-Farber Cancer Institute, and the study’s lead author. She added that combining an effective neoadjuvant treatment with prostatectomy “would increase cure rates in a population at high risk for dying from prostate cancer.”

Taplin et al’s study involved 56 patients with localized high-risk prostate cancer. Eligibility criteria included stage T3 or T4 disease, a Gleason score ≥8, a prostate-specific antigen (PSA) level ≥20, or a PSA velocity >2 ng/mL/year.

The patients were randomized into two groups. One group (n = 27) was treated with the androgen inhibitor leuprolide acetate for 12 weeks, followed by 12 weeks of combination treatment with leuprolide acetate, abiraterone acetate, and low-dose prednisone. The second group (n = 29) received neoadjuvant abiraterone acetate plus leuprolide acetate and prednisone for the entire 24-week period. All 56 patients had radical prostatectomies following their presurgical treatment.

In over one-third of patients who received 24 weeks of abiraterone acetate, postsurgical analysis revealed either complete tumor elimination (10%) or a disease reduction to ≤5 mm of residual cancer (24%). In patients receiving only 12 weeks of abiraterone acetate, complete and partial tumor elimination rates were 4% and 11%, respectively. The treatment was well-tolerated in both groups, with “very low systemic side effects and no additional surgical toxicities,” Taplin noted.

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Discussing the positive response rates, Taplin said, “Historically, the pathological complete response rate with any type of standard hormone therapy is five percent or less. So these rates are very impressive.”

Regarding the possibility of forgoing surgery when complete pathological response is reached in the neoadjuvant setting, Taplin said, “I think we’re relatively far from doing that at this point, but these new hormonal agents look very powerful and that will definitely be an area of investigation.”

Looking ahead, Taplin noted that additional research is needed. “The long-term significance of obtaining a response like this needs to be validated in larger studies,” she said. She also mentioned that a similar trial is being planned that would add a third drug, the androgen receptor antagonist ARN509, to the abiraterone acetate and leuprolide acetate combination.

Abiraterone acetate reduces the production of testosterone, which fuels prostate tumor growth. In April 2011, the FDA approved the drug in combination with prednisone to treat patients with metastatic castration-resistant prostate cancer (mCRPC) following docetaxel-based chemotherapy. Off-label use of abiraterone acetate in chemotherapy-naïve patients with mCRPC is documented, and the FDA may soon approve an indication in this setting following positive results from the phase III COU-AA-302 trial.

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