Neoadjuvant abiraterone helped clear tumors in one-third of men with localized, high-risk prostate cancer in an ongoing randomized phase II trial, investigators report.
At 6 months, a pathological complete response (pCR) or near pCR was achieved by 34% of men given abiraterone (Zytiga) plus prednisone and leuprolide, compared with 15% of men given leuprolide alone (P = .089). Both groups underwent biopsy and further combination therapy with abiraterone, prednisone, and leuprolide before radical prostatectomy.
The 34% response rate is higher than historic controls and unique in the treatment of prostate cancer, where unlike breast and other cancers, neoadjuvant therapies have not shown a benefit to date, Dr. Mary-Ellen Taplin said during a press briefing highlighting research to be presented at the upcoming annual meeting of the American Society of Clinical Oncology (ASCO).
Abiraterone, a highly selective oral CYP17A1 (17 alpha-hydroxylase/C17,20 lyase complex) inhibitor, was approved last September, for use in combination with prednisone for the treatment of men with metastatic castration-resistant prostate cancer previously treated with chemotherapy containing docetaxel (Taxotere).
Dr. Taplin, a medical oncologist at the Dana-Farber Cancer Institute in Boston, said the long-term significance of obtaining a complete response needs to be validated in large, randomized trials, but characterized the response rates as "very impressive given the high-risk features of these patients."
Notably, 71% of the 58 patients had a Gleason score of 8-10, 19% had a prostate-specific antigen (PSA) of more than 20 ng/mL, and all had T3 or T4 disease on prostate exam.
Presscast moderator Dr. Nicholas Vogelzang, cochair of the genitourinary committee for U.S. Oncology and the Southwestern Oncology Group, remarked that "This is one of the first, if not the first study, to show that you can make prostate cancer in the prostate gland itself disappear in a reproducible number of patients.
"This is reminiscent of what we see with rectal cancer when we give chemotherapy and radiation prior to surgery and this is what has now become a standard for breast cancer. Theoretically, at least in the breast cancer literature, when you get a complete disappearance in the primary disease, the outcomes are much better than historically."
When asked whether the current data will push clinicians to use abiraterone off-label in earlier-stage disease, Dr. Taplin said it’s unlikely based on results from a safety trial and the cost of the drug at roughly $7,000/month.
The trial enrolled patients with newly diagnosed intermediate and high-risk prostate cancer with at least three positive biopsies and either a Gleason score of 7 or more, stage T3 disease and a PSA of at least 20 ng/mL or a PSA velocity of more than 2 ng/mL per year. Their median age was 58 years.
The men were randomized to 12 weeks of abiraterone 1,000 mg/day plus prednisone 5 mg/day and leuprolide 22.5 mg or leuprolide 22.5 mg alone. A prostate biopsy was then performed and the men received 12 additional weeks of the triple-combination therapy followed by radical prostatectomy.
A pCR was observed in 10% of the 29 men given all 24 weeks of combination abiraterone and 4% of the 27 men given only 12 weeks of the combination therapy (P = .33), Dr. Taplin said.
A near CR, defined by tumor size of 5 mm or less, was reported in 24% and 11% of patients, respectively.
When asked whether patients with a pCR could forgo surgery, Dr. Taplin said it’s possible, but that it would take a very carefully designed trial to make that leap at this point.
"We’re relatively far from doing this at this point, but these drugs, these new hormonal agents are very powerful and it will definitely be an area of investigation," she said.
The neoadjuvant therapy resulted in low systemic and surgical toxicity. Grade 3 adverse events included elevated AST/ALT in 9% and hypokalemia in 5% of all patients. No grade 4 mineralocorticoid-related adverse events were observed.
"We were able to prove in this study that half the amount of prednisone given in more advanced patients – that is just 5 mg/day – prevented any side effects from abiraterone and may reduce the use of higher doses of steroids in all patients being treated with this drug," Dr. Taplin said.
She noted that a similar trial is being planned that would add the novel androgen-receptor antagonist ARN509 to abiraterone and leuprolide, while a second study is ongoing investigating abiraterone and the experimental hormone drug MDV3100 in this group of patients.
The abstract can be viewed at www.abstract.asco.org and will be formally presented at ASCO on June 2 (Abstract 4521).