Johnson & Johnson’s targeted oral androgen biosynthesis inhibitor, abiraterone acetate, can improve overall survival by nearly four months on average compared with placebo in patients with metastatic advanced prostate cancer, results from a Phase III clinical trial have shown.

The data from a pre-specified interim analysis of the 1,195-patient COU-AA-301 study, presented yesterday at the 35th annual European Society for Medical Oncology (ESMO) congress in Milan, Italy, fleshed out the significant survival benefit and acceptable safety profile reported by J&J in mid-September.

At that point, the company unblinded the COU-AA-301 trial on the recommendation of its Independent Data Monitoring Committee, which also said patients in the placebo arm should be offered treatment with the combination of abiraterone acetate and low-dose prednisone/prednisolone.

J&J now plans to file approval applications for abiraterone, originally discovered by Professor Mike Jarman and colleagues at what is now the Cancer Research UK Cancer Therapeutics Unit at Britain’s Institute of Cancer Research (ICR), in the US and Europe by the end of this year. Applications in the rest of the world will follow, according to local regulatory requirements, J&J said.

If approved, abiraterone acetate will be commercialised and distributed by Centocor Ortho Biotech Inc in the US and by Janssen Pharmaceutical Companies in the rest of the world. J&J scooped up the drug last year through its US$970 million acquisition of Cougar Biotechnology, which had licensed abiraterone from UK life sciences company BTG.

36% survival improvement

The Phase III COU-AA-301 trial was conducted in 147 centres across 13 countries.  Patients with metastatic advanced prostate cancer previously treated with docetaxel chemotherapy were randomly assigned 2:1 to abiraterone acetate (1,000 mg once daily) plus prednisone/prednisolone (5 mg twice daily) – a total of 797 patients – or placebo plus prednisone/prednisolone (398 patients). Overall survival was the primary endpoint.

In the interim analysis, patients treated with abiraterone showed a 35% reduction in the risk of death and a 36% increase in median survival (14.8 months versus 10.9 months) compared with placebo. There were also significant improvements in secondary endpoints among the abiraterone patients. Time to PSA progression was a median 10.2 months versus 6.6 months in the placebo group, while radiographic progression-free survival increased from an average 3.6 months to 5.6 months.

Total PSA response, defined as greater than or equal to a 50% reduction from baseline, was achieved in 38% of patients on abiraterone acetate and in 10% of the prednisone/prednisolone plus placebo group. 

“Abiraterone acetate has the potential to meet a significant unmet need, so this news will be incredibly important to prostate cancer patients and their families,” commented Dr Johann de Bono of the ICR, who was one of the lead COU-AA-301 investigators. 

The results were “extremely exciting because men with this aggressive type of prostate cancer currently have very few treatment options and a poor prognosis”, de Bono noted.

Choice of treatment

According to lead Datamonitor analyst Andrew Paramore, the “fact that abiraterone gives results in patients that have been heavily pre-treated with antihormonal therapies and chemotherapies is striking in itself, as very few agents have been effective beyond the first-line setting”.
Nonetheless, Paramore cautioned, choosing when and in which patients to use the drug will be “a difficult task as two other drugs, Jevtana (carbazitaxel; Sanofi-Aventis) and Provenge (sipuleucel-T; Dendreon), have also shown a survival advantage, albeit in different subsets of patients”.
Two possible treatment scenarios now arise, Paramore suggested: combining the new agents with each other or with other currently approved agents “in the hope of producing additional survival benefits”, or sequential use of these therapies “with the aim of making prostate cancer a chronic disease”.  
Whatever the approach taken, “all three agents will vie for first-line use”, the analyst added. “However, it is likely that abiraterone will be investigated and eventually used following the failure of existing hormone therapies before patients are treated with either Provenge or chemotherapies (Taxotere and Jevtana). Physicians’ familiarity with antihormonal agents and their perceived tolerability will favour this scenario.”