Abiraterone Acetate Significantly Improves Overall Survival of Patients with Post-Chemotherapy Metastatic Castration-Resistant Prostate Cancer

Findings Published Today in The New England Journal of Medicine

TORONTO, May 26, 2011 – A study published today in The New England Journal of Medicine in patients with metastatic advanced prostate cancer following chemotherapy who were treated with abiraterone acetate plus prednisone/prednisolone showed a significant improvement in overall survival compared to patients treated with prednisone/prednisolone plus placebo. The study was sponsored by Ortho Biotech Oncology Research & Development, Unit of Cougar Biotechnology, Inc., an affiliate of the Janssen Pharmaceutical Companies.

The randomized, placebo-controlled Phase 3 study, COU-AA-301, evaluated whether the investigational agent abiraterone acetate, an androgen biosynthesis inhibitor, improves overall survival in patients with metastatic castration resistant prostate cancer (CRPC) – also defined as metastatic prostate cancer – whose disease had progressed following chemotherapy.

Androgens are hormones that promote the development and maintenance of male sex characteristics.1 However, in prostate cancer, androgens can help fuel the tumor’s growth.2 Androgen production primarily occurs in the testes and adrenal glands; in men with prostate cancer, the tumor tissue is an additional source of androgens.3 Abiraterone acetate is an oral androgen biosynthesis inhibitor that works by selectively inhibiting the CYP17 enzyme complex, which is required for the production of androgens at these three sources.4

After a median follow-up of 12.8 months, overall survival for the group receiving abiraterone acetate plus prednisone/prednisolone was 14.8 months vs. 10.9 months for placebo plus prednisone/prednisolone (representing a 36 per cent increase in median survival). Treatment with abiraterone acetate also resulted in a 35 per cent reduction in the risk of death (HR=0.646; 95 per cent CI: 0.543, 0.768; p<0.0001) compared with placebo. This study included 1,195 patients, including 154 Canadian patients, with metastatic CRPC who were previously treated with one or two chemotherapy regimens, at least one of which contained docetaxel.

The study investigators stated that, overall, despite the advanced age and level of frailty in the treatment population, patients had high compliance with abiraterone acetate treatment, for which the toxicities were in general manageable and in some cases reversible.5

“Given that men with metastatic advanced prostate cancer have few options, we are pleased with the results of this rigorous study which show that abiraterone acetate may extend survival in these patients,” said Johann S. de Bono, MD, FRCP, MSc, PhD, The Institute for Cancer Research, The Royal Marsden NHS Foundation Trust, and lead author. “The data indicate that abiraterone acetate has the potential to meet a significant unmet need for advanced prostate cancer patients and their families.”

Men who received abiraterone acetate and prednisone/prednisolone also showed significant improvements in secondary study endpoints when compared to the prednisone/prednisolone plus placebo group: time to PSA progression (TTPP) [median 10.2 months for abiraterone acetate vs. 6.6 months for placebo, HR=0.580 (95 per cent CI: 0.462, 0.728); p<0.0001] and an increase in radiographic progression-free survival (rPFS) [median 5.6 months for abiraterone acetate vs. 3.6 months for placebo, HR=0.673 (95 per cent CI: 0.585, 0.776); p<0.0001].

Total confirmed PSA response, defined as greater than or equal to a 50 per cent decrease from baseline, was achieved in 29 per cent of patients treated with abiraterone acetate vs. 6 per cent in the prednisone/prednisolone plus placebo group [p<0.0001].

“In 2011, there will be more than 25,000 men diagnosed with prostate cancer in Canada, and over 4,000 men will die from it,”6 said Dr. Kim Nguyen Chi, an investigator and author on the study, and medical oncologist at the BC Cancer Agency and the Vancouver Prostate Centre, Vancouver, British Columbia. “The findings of this Phase 3 study of abiraterone acetate are an important development for this group of patients who are in need of more effective treatment options.”

Patients in the abiraterone acetate group experienced more mineralocorticoid-related adverse events than those in the prednisone/prednisolone plus placebo group. The most common adverse events were fluid retention (31 per cent vs. 22 per cent), hypertension (10 per cent vs. 8 per cent) and hypokalemia (17 per cent vs. 8 per cent). Grade 3/4 hypokalemia and hypertension were more frequent in the abiraterone acetate arm than in the placebo arm (3.8 per cent vs. 0.8 per cent and 1.3 per cent vs. 0.3 per cent, respectively). Liver function test abnormalities were observed in 10 per cent of abiraterone acetate-treated patients compared to 8 per cent in the prednisone/prednisolone plus placebo group. Cardiac disorders were observed in 13 per cent of abiraterone acetate patients vs. 10 per cent of patients who received placebo (may not be reversible).

The Independent Data Monitoring Committee (IDMC) recommended unblinding this Phase 3 study at interim analysis, as these results exceeded the preplanned stopping criteria. Furthermore, the IDMC recommended that patients in the prednisone/prednisolone plus placebo group be offered treatment with abiraterone acetate.

The results of this randomized, double-blind, placebo-controlled study were also presented in part during a late-breaking presentation at the Presidential Symposium at the 35th Annual European Society for Medical Oncology (ESMO) Congress in Milan, Italy on October 11, 2010.

Study Design
This randomized, double-blind placebo-controlled Phase 3 study was conducted in 147 centers in 13 countries, including in 12 centres in Canada. Patients with metastatic advanced prostate cancer previously treated with docetaxel (N=1,195) were randomly assigned 2:1 to receive abiraterone acetate (1000 mg once daily) plus prednisone/prednisolone (5 mg twice daily) (N=797), or placebo plus prednisone/prednisolone (N=398). The primary endpoint was overall survival.
 

About Abiraterone Acetate
Abiraterone acetate is an investigational, oral medication being developed for the treatment of men with metastatic advanced prostate cancer (castration resistant prostate cancer) who have received prior chemotherapy containing a taxane.

Abiraterone acetate received approval from the U.S. Food and Drug Administration on April 28, 2011. In December 2010, Janssen Inc. filed a New Drug Submission (NDS) to Health Canada for the investigational drug abiraterone acetate administered with prednisone or prednisolone for the treatment of metastatic advanced prostate cancer in patients who have received prior chemotherapy containing a taxane.
About Metastatic Advanced Prostate Cancer
Metastatic castration-resistant prostate cancer or CRPC occurs when cancer has metastasized beyond the prostate and disease progresses despite serum testosterone below castrate levels.7

The prostate is a gland located around the urethra (under the bladder) in men that produces part of the seminal fluid.8 In some cases, cancer of the prostate can grow slowly compared with other cancers. However, depending on factors including characteristics specific to the patient and the tumor, prostate cancer also can grow very quickly and spread widely.9

Prostate cancer is the most common cancer among men in Canada (excluding non-melanoma skin cancer). It is estimated that approximately 25,500 men will be diagnosed with prostate cancer in Canada in 2011, and one in seven Canadian men will develop prostate cancer during his lifetime.10 The incidence rate of prostate cancer has been increasing since 1980, likely due to an increased rate of early detection and the aging population since the chances of developing prostate cancer increases with age.11 But according to Prostate Cancer Canada, prostate cancer is turning up in men in their 40s.12

While 90 per cent of prostate cancer cases are curable if detected and treated early,13 it is estimated that 4,100 Canadian men will die of the disease in 2011.14 On average, 80 Canadian men will die of prostate cancer every week.15 Fortunately, death rates have been declining since the mid-1990s, which is likely due to early detection, better treatment or both.16

Disclaimer
Please be advised that the data presented represents clinical trial results only and that abiraterone acetate is not approved in Canada.


About Janssen Inc.
As a member of the Janssen Pharmaceutical Companies, Janssen Inc. is dedicated to addressing and solving the most important unmet medical needs in pain management, psychiatry, oncology, immunology, psoriasis, virology, anemia, attention deficit hyperactivity disorder, gastroenterology and women’s health. Driven by our commitment to the passionate pursuit of science for the benefit of patients, we work together to bring innovative ideas, products and services to patients around the world.

About the Ortho Biotech Oncology Research & Development, Unit of Cougar Biotechnology, Inc.
Ortho Biotech Oncology Research & Development, Unit of Cougar Biotechnology, Inc. partners with affiliated units and companies in the Janssen Pharmaceutical Companies in the research and development of oncology and supportive care treatments.

# # #

For more information or to arrange an interview with a spokesperson, please contact:

Jennifer McCormack Laine Jaremey
Janssen Inc. MSL Canada
416-382-5044 416-847-1321
jmccorm3@its.jnj.com laine.jaremey@mslgroup.com

1 National Cancer Institute. Dictionary of Cancer Terms – Androgen. Available at: http://www.cancer.gov/dictionary?CdrID=45592.
2 American Cancer Society. Cancer Facts & Figures 2010. Atlanta: American Cancer Society; 2010.
3 ZYTIGA (abiraterone acetate) Draft Label. November 2010.
4 ZYTIGA (abiraterone acetate) Draft Label. November 2010.
5 de Bono JS, Logothetis CJ, et al. Survival In Metastatic Prostate Cancer Treated with Abiraterone Acetate. New England Journal of Medicine. DRAFT MANUSCRIPT
6 Prostate Cancer Statistics. Canadian Cancer Society. Available at: http://www.cancer.ca/Canada-wide/About%20cancer/Cancer%20statistics/Stats%20at%20a%20glance/Prostate%20cancer.aspx?sc_lang=en. Accessed May 19, 2011.
7 Hotte SJ, Saad F. Current management of castrate-resistant prostate cancer. Curr Oncol. 2010 September; 17(Supplement 2): S72–S79.
8 An Introduction to Prostate Cancer. Prostate Cancer Foundation. 2009. Available at: http://www.prostatecancerfoundation.org/atf/cf/{705B3273-F2EF-4EF6-A653-E15C5D8BB6B1}/IntroProstateCancer.pdf. Accessed November 2009.
9 Mayo Clinic. “Prostate Cancer.” http://www.mayoclinic.com/health/prostate-cancer/DS00043. Accessed September 10, 2010.
10 Prostate Cancer Statistics. Canadian Cancer Society. Available at: http://www.cancer.ca/Canada-wide/About%20cancer/Cancer%20statistics/Stats%20at%20a%20glance/Prostate%20cancer.aspx?sc_lang=en. Accessed August 2010.
11 Prostate Cancer Statistics. Canadian Cancer Society. Available at: http://www.cancer.ca/Canada-wide/About%20cancer/Cancer%20statistics/Stats%20at%20a%20glance/Prostate%20cancer.aspx?sc_lang=en. Accessed May 19, 2011.
12 Statistics. Prostate Cancer Canada. Available at: http://www.prostatecancer.ca/Prostate-Cancer/Prostate-Cancer/Statistics.aspx. Accessed August 2010.
13 Statistics. Prostate Cancer Canada. Available at: http://www.prostatecancer.ca/Prostate-Cancer/Prostate-Cancer/Statistics.aspx. Accessed August 2010.
14 Prostate Cancer Statistics. Canadian Cancer Society. Available at: http://www.cancer.ca/Canada-wide/About%20cancer/Cancer%20statistics/Stats%20at%20a%20glance/Prostate%20cancer.aspx?sc_lang=en. Accessed May 19, 2011.
15 Prostate Cancer Statistics. Canadian Cancer Society. Available at: http://www.cancer.ca/Canada-wide/About%20cancer/Cancer%20statistics/Stats%20at%20a%20glance/Prostate%20cancer.aspx?sc_lang=en. Accessed May 19, 2011.
16 Statistics. Prostate Cancer Canada. Available at: http://www.prostatecancer.ca/Prostate-Cancer/Prostate-Cancer/Statistics.aspx. Accessed May 19, 2011.
 

Posted: May 2011

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