Abiraterone acetate, an experimental agent, may benefit men with metastatic castration-resistant PCa.

CHICAGO—An experimental oral agent called abiraterone acetate, used in combination with prednisone, can decrease serum androgen levels to undetectable levels in men who have progressive metastatic castration-resistant prostate cancer (CRPC) following failure of docetaxel-based chemotherapy, according to new data.

“This drug is specifically designed to block androgen synthesis,” said investigator Howard Scher, MD, chief of genitourinary oncology services at Memorial Sloan-Kettering Cancer Center in New York.

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“It has been shown in model systems that another way prostate cancers escape is that they learn how to make their own androgens. It has also been shown that the conventional methods we use to lower androgens do not completely lower androgens within the prostate itself. So this [new agent] will bring the level of androgens significantly lower.”

Dr. Scher and his colleagues studied the use of abiraterone acetate in combination with prednisone in patients with metastatic CRPC that had progressed despite docetaxel-based chemotherapy. All men received oral abiraterone acetate 1,000 mg and prednisone (5 mg twice a day) in 28-day cycles.

The primary end point was a 50% or greater decline in PSA levels from baseline. The investigators also monitored changes in bone and soft tissue disease as well as pre- and post-treatment circulating tumor cell (CTC) numbers.

A total of 43 patients was screened; 38 patients were eligible for treatment. The median age of the subjects was 73 years and the median PSA level was 86.3 ng/mL. A total of 32 subjects (84%) had a CTC count of 5 or more per 7.5 mL of blood at baseline. A total of 26 subjects (68%) had received one course of chemotherapy, and 12 patients (32%) had received two courses. The sites of metastases were bone in 10 patients (26%), bone and lymph nodes in 15 (39%), and bone and viscera in 11 (29%). Two patients had metastases in soft tissue but no bone disease.

Of the 38 patients, 35 were evaluable. Eleven (31%) had disease progression within three months of starting treatment. Nine patients (26%) had disease progression within six months, and two had disease progression after six months. Seven patients remained on treatment for three to six months and six remain on treatment for six months or longer.

At three months, 14 of the 35 patients (40%) had achieved a decline of 50% or greater in PSA levels from baseline. The CTC counts decreased to fewer than 5 cells per 7.5 mL of blood after therapy in 11 patients; CTC counts remained greater than 5 cells per 7.5 mL in 21 patients. Fifteen of these 21 patients had disease progression.

“This is an example of a hormonal agent working both in patients who have failed hormones as well as in patients who have failed chemotherapy,” said Dr. Scher, who reported study findings here at the American Society of Clinical Oncology annual meeting. “So the decision to administer chemotherapy does not necessarily mean that the cancer can’t respond to a hormonal agent.”

The investigators observed no grade 3 or 4 hypertension or hypokalemia, but one patient discontinued treatment because of transaminitis and myositis. In general, the new drug appeared to be well tolerated, Dr. Scher said.