Wednesday 25 May 2011
The drug abiraterone acetate gave men with advanced prostate cancer an average of four months of extra life, according to Phase III trial results published in the New England Journal of Medicine today.
Abiraterone acetate, trade name Zytiga™, was discovered at The Institute of Cancer Research (ICR) in what is now the Cancer Research UK Cancer Therapeutics Unit. It was first trialled at The Royal Marsden Hospital.
The success of an anti-hormone therapy in men with late stage prostate cancer challenges conventional wisdom, opening the door to an entirely new way of treating these patients.
“Men with advanced prostate cancer have very few therapies available to them* and sadly around 10,000 patients in the UK die each year from this disease,” says Chief Investigator and lead author Professor Johann de Bono from the ICR and The Royal Marsden. “We are thrilled that a drug discovered at The Institute of Cancer Research has been proven to significantly extend life for many men, giving doctors a valuable new treatment option.”
The positive study results led the US Food and Drug Administration (FDA) on April 28 to approve abiraterone acetate as a pill in combination with the steroid prednisone for men with late-stage “castration-resistant**” prostate cancer who have received prior docetaxel chemotherapy.
The drug’s manufacturer Janssen Pharmaceutical Companies has also applied for regulatory agency approvals in Europe, but for now the drug is not available to patients in the UK.
Prostate cancer growth is fuelled by the male hormone testosterone. Hormone treatments that reduce the testes’ production of testosterone usually stop benefiting patients after a few years, leading to the assumption that as tumours progressed they developed the ability to grow independently of testosterone.
However it was known that the adrenal glands also produce testosterone, suggesting that this was providing fuel to some cancer cells. In addition, scientists elsewhere had measured higher levels of enzymes involved in testosterone synthesis inside prostate tumour tissue, giving rise to a new theory that some cancers were able to produce their own testosterone.
Professor Mike Jarman and his team in what is now the Cancer Research UK Cancer Therapeutics Unit at the ICR in Sutton, south of London, designed abiraterone acetate to have a different mechanism of action from standard hormone treatments – blocking the production of male hormones in all tissues, not just the testes, by targeting an enzyme involved in hormone synthesis called CYP17.
“From the success of this study, it’s now clear that men with advanced prostate cancer can still benefit from treatments targeting male hormones. This has corrected 40 years of misunderstanding about this disease and we hope it will lead to the development of more second-line hormone treatments for these men – much like those used successfully to treat breast cancer,” ICR Chief Executive Professor Alan Ashworth says.
The randomised, double-blind study sponsored by Ortho Biotech Oncology Research & Development, a Unit of Cougar Biotechnology, Inc., began in May 2008 and was conducted in 147 sites in 13 countries. The 1,195 men who enrolled in the trial had all stopped responding to standard hormone therapy as well as second-line treatments including the chemotherapy drug docetaxel. They were either given abiraterone acetate together with the steroid prednisone (797 men), or prednisone and a placebo (398 men).
The study was designed to assess overall survival (the “primary endpoint”) and showed that men given the placebo survived an average of 11 months, while men given abiraterone acetate survived for nearly 15 months. Pain eased during the trial for a much greater number of patients taking abiraterone acetate than the placebo (44 per cent versus 27 per cent in patients for whom this could be measured).
Based on results of a prespecified interim analysis of the study, the trial’s Independent Data Monitoring Committee recommended unblinding the trial and allowing anyone on the placebo arm to be offered the drug.
The scientists also examined other possible measures of a drug’s effectiveness (as “secondary endpoints”). When compared to the placebo group, patients taking abiraterone acetate were also more likely to experience a significant drop in their prostate specific antigen (PSA) levels, the standard measure of prostate cancer activity (29 per cent versus six per cent), and they had more time before their PSA level started to rise again (10.2 months versus 6.6 months). X-rays showed mean time until tumour growth among the treatment group was also longer (5.6 months versus 3.6 months).
Doctors reported that patients taking abiraterone acetate generally did not experience some of the unpleasant side-effects they often observe in men being treated with chemotherapy. In this trial, patients in the abiraterone acetate group compared to the placebo group did report more side-effects such as fluid retention and swelling related to elevated levels of the mineralocorticoid class of steroid hormones, but these could usually be managed.
Harpal Kumar, Cancer Research UK’s chief executive, said: “Abiraterone is the first treatment of its kind shown to be effective in men with this type of advanced prostate cancer. This could make a huge difference to the 10,000 men diagnosed with aggressive forms of the disease in the UK every year. Thanks to our supporters, Cancer Research UK was a major funder of the discovery and early development of abiraterone including the first studies in humans. It’s incredibly heartening to see this early potential being turned into a treatment capable of providing patients with valuable extra months of life.”
Media Contact: ICR Science Communications Manager Jane Bunce on 0207 153 5106 or after hours 077217 47900
Notes to editors:
Abiraterone acetate is not currently available in the UK.
* In men with advanced prostate cancer, only three other drugs have been shown to prolong survival – chemotherapy drugs docetaxel and cabazitaxel and the immunotherapy drug Sipuleucel.
** The castration-resistant form of the disease is prostate cancer that continued to grow while the patient was receiving standard therapy to lower their testosterone levels.
Prostate cancer has overtaken lung cancer to become the most common cancer in men. One man dies of prostate cancer in the UK every hour, and more than 35,000 men are diagnosed with the disease every year. Prostate cancer is considered to be advanced once it has spread beyond the prostate region.
Abiraterone was discovered at the ICR in research supported by grants from Cancer Research Campaign (now Cancer Research UK), the Medical Research Council (MRC) and BTG International LTD. Subsequent patient trials and further research on abiraterone was supported by Cougar Biotechnology Inc. / Janssen Pharmaceutical Companies, Cancer Research UK, Experimental Cancer Medicine Centre, the MRC, BTG International Ltd, Prostate Cancer Foundation, Prostate Cancer Research Foundation, The Prostate Cancer Charity, the ICR and The Royal Marsden. Cancer Research Technology assigned abiraterone acetate to BTG International Ltd, who in turn licensed it to Ortho Biotech Oncology Research & Development, a unit of Cougar Biotechnology Inc., now a member of the Janssen Pharmaceutical Companies.
The Institute of Cancer Research (ICR)
- The ICR is Europe’s leading cancer research centre.
- The ICR has been ranked the UK’s top academic research centre, based on the results of the Higher Education Funding Council’s Research Assessment Exercise.
- The ICR works closely with partner The Royal Marsden NHS Foundation Trust to ensure patients immediately benefit from new research. Together the two organisations form the largest comprehensive cancer centre in Europe.
- The ICR has charitable status and relies on voluntary income, spending 90 pence in every pound of total income directly on research.
- As a college of the University of London, the ICR also provides postgraduate higher education of international distinction.
- Over its 100-year history, the ICR’s achievements include identifying the potential link between smoking and lung cancer which was subsequently confirmed, discovering that DNA damage is the basic cause of cancer and isolating more cancer-related genes than any other organisation in the world.
- The ICR is home to the world’s leading academic cancer drug development team. Several important anti-cancer drugs used worldwide were synthesised at the ICR and it has discovered an average of two preclinical candidates each year over the past five years.
For more information visit www.icr.ac.uk
The Royal Marsden Hospital
The Royal Marsden was the first hospital in the world dedicated to cancer diagnosis, treatment and research into the causes of cancer. Today, as The Royal Marsden NHS Foundation Trust, together with its academic partner The Institute of Cancer Research, form the largest comprehensive cancer centre in Europe with over 40,000 patients from the UK and abroad seen each year. It is a centre of excellence, and was the only NHS Trust to achieve the highest possible ranking in the Healthcare Commission’s Annual Health Check for four year in a row. Prince William became President of The Royal Marsden in 2007, following a long royal connection with the hospital.
Cancer Research UK
- Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research
- The charity’s groundbreaking work into the prevention, diagnosis and treatment of cancer has helped save millions of lives. This work is funded entirely by the public.
- Cancer Research UK has been at the heart of the progress that has already seen survival rates double in the last forty years.
- Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses.
- Together with its partners and supporters, Cancer Research UK's vision is to beat cancer.
For further information about Cancer Research UK's work or to find out how to support the charity, please call 020 7121 6699 or visit www.cancerresearchuk.org