Author:

Simon Crompton

Abstract

Before abiraterone was approved for use in 2011, the prospect of long-term survival for men with advanced prostate cancer was slim. The growth of prostate cancers is driven by male hormones – so when the cancer has spread beyond the prostate capsule and surgical treatments become impossible, the best option is to retard growth by depriving the cancer of its supply of androgens.

This was traditionally achieved though drugs or surgery preventing the testes releasing testosterone into the body. However, with time, prostate cancers seem to become ‘resistant’ to this kind of hormone treatment and continue their growth.

In the 1990s, work by biochemists at the Cancer Research UK Therapeutics Unit, at the Institute of Cancer Research in the UK, resulted in conventional ideas of ‘resistance’ being turned on their head. They explored alternative hypotheses for why androgen deprivation therapy was time-limited, and developed a new type of compound that blocked the root cause: androgen production in parts of the body beyond the testes.

Subsequent development of the chemical into a usable drug led to the compound being included in the ground-breaking STAMPEDE trials, headed by the Institute of Cancer Research and The Royal Marsden Hospital in the first decade of the 21st century. The successful results led to abiraterone being approved in the United States and Europe for use in men with castration-resistant prostate cancer in 2011.

STAMPEDE results show that 83% of those receiving abiraterone alongside androgen deprivation therapy survived for over three years, compared to 76% of men who received androgen deprivation therapy alone. They also show that abiraterone slows growth of high-risk cancers and prolongs life when prescribed before the cancer has spread beyond the prostate.

Abiraterone has since become a standard of care for advanced prostate cancer, improving survival and reducing the chance of progression for hundreds of thousands of men worldwide.

Background

In the 1940s, Canadian-American surgeon Charles Huggins discovered that surgical removal of the testes resulted in depletion of androgens (mainly testosterone and dihydrotestosterone), and a corresponding regression of prostate cancer. He went on to pioneer the use of hormones to control the spread of some cancers, leading to the development of androgen deprivation therapy (ADT) in prostate cancer. In the early days, the principal therapy was diethylstilbestrol, a synthetic, nonsteroidal oestrogen. However, this was associated with some unpleasant as well as serious side effects, including raised risk of thromboembolism and heart attack.

The 1970s and 1980s saw the development of GnRH/LHRH agonists such as leuprolide and goserelin, which aimed to stop the testes producing male sex hormones (androgens) by blocking signals from the pituitary gland.

ADT can slow and control cancer tumour growth and has become the standard treatment – sometimes alongside radiotherapy and drugs – for prostate cancer that has spread or is at high risk of returning.

However, although ADT can control prostate cancer for years, its effect is time-limited. The disease eventually progresses and patients have to turn to other life-extending treatments such as chemotherapy, which can bring significant side effects. After that, often the patient’s only option is supportive care.

In the 1990s, researchers at the Institute of Cancer Research near London joined the search to find out why men became ‘resistant’ to ADT, and whether there might be other ways of controlling the hormones that drive prostate cancer growth.

Early research into a new chemical

In the 1990s, Mike Jarman, Elaine Barrie and Gerry Potter, at the Cancer Research UK Cancer Therapeutics Unit at the Institute of Cancer Research, began investigating new ideas about why ADT stopped working. Many scientists believed that cancers somehow learned to grow without testosterone from the testes. As a result, the term ‘hormone refractory’ had become commonly used to describe cancers that no longer responded to ADT.

The Cancer Research UK team began working on an alternative theory: that these prostate cancers started growing again not because they were resistant to the hormones but because they were using hormones from elsewhere in body. If they could disrupt the synthesis of testosterone throughout the body, that might prevent tumour growth even when conventional ADT failed.

The team set out to design drugs to block an enzyme called CYP17, which was known to help in the production of male sex hormones. A drug that inhibited that enzyme – ketoconazole – already existed, but research had shown it to have limited effectiveness against prostate cancer.

Using computerised modelling to work out how molecules would fit together in three dimensions, Elaine Barrie and Gerry Potter evaluated a number of compounds made within Mike Jarman’s lab, assessing how selectively they might inhibit CYP17. They arrived upon a chemical called CB7598, which soon became converted into a drug for trialling, named abiraterone acetate. Early research showed that abiraterone could specifically and irreversibly block CYP17 in cells in the lab, and then in animals with cancer, with subsequent decreases in the size of androgen-dependent organs (Potter et al., 1995).

From 1996, the first small clinical trials in prostate cancer patients took place at several hospitals, led by Ian Judson at the Royal Marsden Hospital, which partners with the Institute of Cancer Research. They showed that abiraterone did hit the correct target and lower levels of male androgens without short-term side effects.

An unfortunate pause

At this crucial point, as the 21st century dawned, the development of abiraterone stalled.

Despite the drug’s initial promise, some researchers feared that it might provoke a potentially serious side-effect called adrenal insufficiency, where the adrenal glands are unable to produce sufficient cortisol for the body.

There was also a lack of enthusiasm from some clinicians and researchers who believed that blocking androgen production at a late stage in cancer progression might have limited effectiveness.

Malcolm Mason, whose patients at the Velindre Cancer Centre in Cardiff, Wales, took part in the earliest trials, recalled having doubts about the survival gain.

“At that time, we already used a combination of drugs, which suppressed both testosterone production by the testicles and also the extra 10 per cent of testosterone produced elsewhere,” he said, (Scowcroft, 2015). “But the extra gain in survival with this combination, compared with suppressing testicular testosterone alone, was very small. So we wondered how a single drug that effectively did the same as this combination would give any greater benefit than what we had already.”

And amid excitement about new targeted therapies for cancer, hormone therapies seemed old-fashioned. Drug companies weren’t very enthused, Ian Judson recalled, and no one was rushing to publish the abiraterone trial results. “I’ve still got a rejection letter in a box file somewhere,” said Judson. “The reviewers asked: ‘Why would anyone think that further suppression of testosterone would be effective in prostate cancer that has already become resistant?’,” (Scowcroft, 2015).

It wasn’t until 2004 that the trial results were finally published, in the British Journal of Cancer (O’Donnell et al., 2004). By that time, a new discovery had begun to change everything.

A new momentum

In the early 2000s, US laboratories discovered that, as prostate cancers grow, they begin producing their own supply of testosterone. Even in the presence of hormone-blocking drugs, they could fuel themselves.

The discovery knocked on the head the idea that prostate cancers became ‘resistant’ to male hormones. Far from it: they remained so dependent that they produced the hormones themselves. A drug that inhibited all pathways involved in testosterone production, including from the tumour itself, clearly had a place.

Johann de Bono joined the Institute of Cancer Research from the University of Texas Health Science Center, San Antonio, to pick up the work on abiraterone in 2003. He started from the basis that late-stage prostate cancer was not ‘hormone resistant’ or ‘hormone refractory’ but ‘castration resistant’ – a change of terminology which reflected developing knowledge in prostate cancer.

“This new understanding meant that drugs like abiraterone, designed to directly block hormone production instead of just the testosterone produced by the testicles, were suddenly very promising,” said de Bono – a medical oncologist born Malta and trained in Glasgow, who is now Regius Professor of Cancer Research and a Professor in Experimental Cancer Medicine at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust (ICR News, 2023).

In 2004, the Institute gained the financial backing it needed from Los Angeles-based Cougar Biotechnologies (later acquired by Johnson & Johnson) to run the clinical trials required to prove the drug’s efficacy and safety.

A phase I/II study of 54 patients confirmed earlier results, showing that up to 70% of men responded to abiraterone. They experienced significant benefits for an average of eight months, with scans showing their tumours decreased in size and their PSA levels (used as a marker for prostate cancer) dropped substantially.

Then, in 2010, the landmark results of phase III trials of abiraterone were revealed at the European Society for Medical Oncology (ESMO) meeting in Milan (Science Daily, 2010). Johann de Bono announced that patients with metastatic castration-resistant prostate cancer survived four months longer than patients receiving placebo. “These results are likely to alter the standard of care for men with advanced prostate cancer who have progressed despite receiving docetaxel-based chemotherapy, a critically important area of unmet need,” he said.

Final analysis of the trial, published in Lancet Oncology in 2012, showed that patients given abiraterone lived on average 15.8 months longer, compared with 11.2 months for men taking a placebo (Fizazi et al., 2012).

In April 2011, the FDA in the US approved abiraterone acetate in combination with steroids for treatment of patients with late-stage, castration-resistant prostate cancer who have received prior docetaxel chemotherapy. Approval by the European Medicines Agency followed.

The value of the drug to men who were no longer responding to other treatments had been established. But what if the drug had wider applications?

The STAMPEDE trial

Since 2005, the STAMPEDE clinical trial has been exploring the best ways to treat newly-diagnosed advanced prostate cancer. It is this trial, funded by Cancer Research UK and coordinated by the MRC Clinical Trails Unit at University College London, which uncovered some of the abiraterone’s wider value.

STAMPEDE is a large and highly innovative multi-arm multi-stage clinical trial, each arm comparing a new treatment against the current standard hormone treatment. Two parts of the STAMPEDE have focused on abiraterone. They both indicated that using abiraterone at an earlier stage could be beneficial for patients.

The main abiraterone arm, published in 2017, studied the effect of adding abiraterone to standard ADT in men who were starting standard hormone therapy for prostate cancer for the first time (James et al.) Participants were also given a steroid, prednisolone, to counter abiraterone’s side effects.

It found that adding abiraterone to standard ADT at the start of hormone treatment improved survival by 37%. Speaking on the release of the data, Chief Investigator Nick James, Professor of Prostate and Bladder Cancer Research at the Institute of Cancer Research and Consultant Clinical Oncologist at The Royal Marsden NHS Foundation Trust, said: “These are the most powerful results I’ve seen from a prostate cancer trial – it’s a once-in-a-career feeling. This is one of the biggest reductions in death I’ve seen in any clinical trial for adult cancers,” (Glenza, 2017).

The follow-up, published in 2021, built on this study to examine the effect of adding a second drug, enzalutamide, alongside abiraterone (Attard et al.). This time the focus was on cases where the prostate cancer had not spread to other parts of the body but was at high risk of doing so. Although it showed that adding enzalutamide brought little effect, it did show after six years that abiraterone could be an effective way of stopping high-risk cancers that were still localised within the prostate, cutting the risk of dying by 50%.

“Through STAMPEDE, we’ve been the first to show that abiraterone can benefit men whose prostate cancer is at an earlier stage – improving survival and reducing the chance of progression,” said Nick James, (ICR News, 2023). “These and other findings have changed the standard of care worldwide.”

In all, 12,000 men with prostate cancer were involved in the STAMPEDE trial, which was led and devised by Max Parmar, Director of the MRC Clinical Trials Unit at University College London. He has estimated that the findings from STAMPEDE and other contemporaneous trials have pushed median survival of men with metastatic disease from three years in 2005 to seven years today.

Continuing research

Other European studies besides STAMPEDE have developed knowledge about abiraterone’s applications. Trials led by medical oncologist Karim Fizazi at the Institut Gustave Roussy in Paris, have investigated the benefits of using abiraterone straight away (as opposed to waiting until cancers have become ‘resistant’) in men who have newly diagnosed (castration-sensitive) prostate cancer which has metastasised.

LATITUDE, which began enrolment in 2013, was the first phase III trial to examine the survival benefit of adding abiraterone to the standard treatment of ADT plus docetaxel chemotherapy. The final analysis, published in 2019, showed that median overall survival was 53.3 months with abiraterone and 36.5 months without (Fizazi et al., 2019).

PEACE-1, which also began enrolment in 2013, is an international and evolving trial investigating the interplay of various components of current standard care for these men – ADT, docetaxel, other hormonal agents, radiotherapy – with care including abiraterone, either with or without radiotherapy (for more on the PEACE Consortium see also the interview with Karim Fizazi). Results presented at ESMO in 2021 and published in 2022 showed that the addition of abiraterone improved both overall survival and radiographic progression-free survival (Fizazi et al., 2022).

Commenting on the findings, Karim Fizazi said that, “adding abiraterone on top of ADT plus docetaxel very clearly prolongs progression-free survival, and I’m speaking about radiographic progression-free survival.” On overall survival, abiraterone reduced the risk of death by 25%, he said (The Uromigos, 2021).

Patient response and availability

Despite the success of abiraterone in trials, and the consequent inclusion of the drug in international guidelines for treating prostate cancer that is advanced or at high risk of spreading, there have been concerns about availability.

In the UK, for example – where abiraterone was discovered and trialled – there has been anger from patient organisations that, until recently, the National Health Service only funded the use of the drug in patients whose prostate cancer had already spread. The NHS in Scotland and Wales belatedly funded its use for cancers at risk of spreading in 2023, when abiraterone came off patent. Finally, the NHS in England and Northern Ireland followed suit in January 2026. According to the charity Prostate Cancer UK, more than 3,000 lives will be saved in England as a result over the next five years.

Many patients have provided testimony about the impact that abiraterone has made on their lives.

The Institute of Cancer Research has cited the experiences of Alfred Samuels, a patient advocate, author and film maker, who was diagnosed with advanced prostate cancer in January 2012 and was advised by doctors to “think short-term”. He joined the STAMPEDE trial in March of that year, and started treatment with abiraterone and hormone therapy.

In January 2026, he posted on LinkedIn, celebrating 14 years since his diagnosis. “Having metastatic prostate cancer is not automatically a death sentence,” he wrote. “There are treatments. Real treatments. And the treatments we have now are light-years ahead of what existed in January 2012.”

Abiraterone saved his life, he told Institute of Cancer Research in 2023. “It has given many men like me, and their families, extended time together and improved their quality of life. Thanks to the treatment, I have been able to live to meet six grandchildren and play a part in their lives. This importance cannot be overstated. Abiraterone has allowed me to find a new life and reinvent myself as time has progressed.”

References

Attard, G., Murphy, L., Clarke, N.W., Cross, W., Jones, R.J., et al. (2022). Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol. The Lancet, 399, 447–460.

Fizazi, K., Scher, H. I., Molina, A., Logothetis, C.J., Chi, K.N., et al. (2012) Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol, 13, 983–992.

Fizazi, K., Tran, N., Fein, L., Matsubara, N., Rodriguez-Antolin, A. et al. (2019). Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol, 20, 686–700.

Fizazi, K., Foulon, S., Carles, J., Roubaud, G., McDermott, R. et al. (2022). Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design. The Lancet, 399,1695–1707.

Glenza, J. (2017) Prostate cancer trial stuns researchers: 'It's a once in a career feeling'. The Guardian, 3 June 2017. Retrieved from https://www.theguardian.com/society/2017/jun/03/prostate-cancer-therapy-study-abiraterone

ICR News. (2011). A new way to treat prostate cancer: The story of abiraterone. Posted 26 May 2011. Retrieved from https://www.icr.ac.uk/about-us/icr-news/detail/a-new-way-to-treat-prostate-cancer-the-story-of-abiraterone

ICR News. (2023). Over a decade of abiraterone: the drug that revolutionised advanced prostate cancer care. Posted 14 March 2023. Retrieved from https://www.icr.ac.uk/about-us/icr-news/detail/over-a-decade-of-abiraterone-the-drug-that-revolutionised-advanced-prostate-cancer-care

James, N.D., de Bono, J.S., Spears M.R., Clarke, N.W., Mason, M.D., et al. (2017). Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. N Engl J Med, 377, 338–351.

O'Donnell, A., Judson, I., Dowsett, M., Raynaud, F., Dearnaley, D. et al. (2004). Hormonal impact of the 17α-hydroxylase/C17,20-lyase inhibitor abiraterone acetate (CB7630) in patients with prostate cancer. Br J Cancer, 90, 2317–25.

Potter, G., Barrie, S. E., Jarman, M. & Rowlands, M.G. (1995). Novel Steroidal Inhibitors of Human Cytochrome P45017α-(17α-Hydroxylase-C17,20-lyase): Potential Agents for the Treatment of Prostatic Cancer. J Med Chem, 38, 2463–71.

Science Daily. (2010). Abiraterone acetate improves survival in metastatic castration-resistant prostate cancer, trial confirms. Posted 12 October 2010. Retrieved from https://www.sciencedaily.com/releases/2010/10/101012114210.htm

Scowcroft, H. (2015). Our milestones. The birth of abiraterone for prostate cancer. Cancer Research UK News, posted 21 September 2015. Retrieved from https://news.cancerresearchuk.org/2015/09/21/our-milestones-the-birth-of-a-new-prostate-cancer-drug/

The Uromigos. (2021). PEACE-1 Overall Survival in Prostate Cancer. GUOncologyNow (podcast) Episode 137. Posted 19 September 2021. Retrieved from https://www.guoncologynow.com/podcast/episode-137-peace1-overall-survival-in-prostate-cancer

Further reading/listening

Cancer Research UK News. (2017). Adding abiraterone to standard treatment improves cancer survival by 40 per cent. Posted 3 June 2017. Retrieved from https://news.cancerresearchuk.org/2017/06/03/adding-abiraterone-to-standard-treatment-improves-prostate-cancer-survival-by-40-per-cent/

MRC Clinical Trials Unit News. (2025). The STAMPEDE prostate cancer trial wins NIHR Impact Prize. Posted 25 March 2025. Retrieved from https://www.mrcctu.ucl.ac.uk/news/news-stories/2025/march/the-stampede-prostate-cancer-trial-wins-nihr-impact-prize/

MRC Clinical Trials Unit News (2023). STAMPEDE: Impact and legacy (podcast). Posted 10 August 2023. Retrieved from https://www.mrcctu.ucl.ac.uk/news/news-stories/2023/august/new-podcast-episodes-on-the-stampede-prostate-cancer-trial/