Significant Impact for New Prostate Cancer Therapy
Milan—Men with castration-resistant prostate cancer (CRPC) gained 4 months in overall survival (OS) when treated with the novel antiandrogen abiraterone acetate, data from a large randomized trial showed.
Treatment with abiraterone and prednisone led to a median OS of 14.8 months compared with 10.9 months for prednisone alone (P <.001). Although seemingly modest, the difference will likely have a practice changing impact on the treatment of CRPC, lead investigator Johann de Bono, MBBS, PhD, an oncologist at the Royal Marsden Hospital in London, said at the 35th European Society for Medical Oncology Congress.
“In the history of prostate cancer, only 4 drugs have ever shown a survival benefit,” said Dr de Bono.
Some patients treated with the agent have had long-lived responses, including 2 of his own patients who have been treated continuously for more than 4 years.
Abiraterone blocks androgen synthesis by inhibiting the CYP17 rate-limiting enzyme necessary for conversion of testosterone precursors into the male hormone. Laboratory and clinical evidence have suggested that some prostate cancer cells generate intratumoral androgens despite androgen deprivation therapy (ADT), as do the adrenal glands. Abiraterone targets both adrenal and intratumoral androgen biosynthesis.
Response on Multiple End Points
Dr de Bono reported findings from a multicenter study involving 1195 men with CRPC that had proved unresponsive to docetaxel, in addition to conventional ADT. The patients were randomized 2:1 to prednisone plus abiraterone or placebo, and the primary end point was OS.
In addition to the survival advantage, all secondary end points showed superiority for abiraterone acetate over placebo:
• Time to prostate-specific antigen (PSA) progression, 10.2 versus 6.6 months; P <.001
• Radiologically confirmed progression free survival, 5.6 versus 3.6 months; P <.001
• PSA response, 38% versus 10%; P <.001.
Subgroup analysis showed consistent effects of treatment with abiraterone. Patients treatedwith abiraterone had a higher incidence of edema (30.5% vs 22.3%) and hyperkalemia (17.1% vs 8.4%). Abnormal liver function tests and cardiac disorders occurred in a similar proportion of patients in both groups, and grade 3-4 adverse events were uncommon in both groups.
Impressive Results, Expensive Potential
Invited discussant Cora Sternberg, MD, a genitourinary oncologist at Camillo Forlanini Hospital in Rome, said the study yielded “the most impressive results that I’ve seen in a long time, in this patient population.” Abiraterone is the farthest along in development of several new antiandrogens under investigation and could lead the way toward new treatment strategies for CRPC, added Dr Sternberg.
Dr de Bono said the findings create a potential for novel combination strategies, such as abiraterone and the recently approved immunotherapeutic agent sipuleucel-T (Provenge). Such combinations would have substantial cost implications, given the $93,000 price tag for a single course of the sipuleucel-T, which has yet to win approval for Medicare reimbursement