Men with particularly aggressive prostate cancers can be treated more effectively by combining an existing targeted medicine, abiraterone, with a new experimental drug to block two of cancer’s growth signals at once, a major new trial shows.

The new combination extended the time before prostate cancers progressed and spread further in men whose tumours lacked a gene known as PTEN – one of the most commonly deleted tumour suppressor genes in cancer.

A team led by The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust assessed the efficacy of the targeted hormone drug abiraterone – standard medicine for many men with advanced prostate cancer – together with a new drug called ipatasertib in men with advanced prostate cancer who had received no prior treatment.

Previous results looking at ipatasertib’s safety and efficacy in combination with abiraterone had already shown promise, but the latest findings published in The Lancet provide the first strong evidence of the benefit of combining the two drugs.

Longer follow-up will be required before the combination can get regulatory approval or be accessed on the NHS.

The international phase III trial, known as the IPATential150 study, took place across 200 sites in 26 countries and involved 1,101 men, of whom 521 had tumours that lacked a fully functioning PTEN gene.

The trial, funded by Roche, found that giving ipatasertib plus abiraterone as a first-line treatment reduced the risk of death or cancer progression in patients whose tumours lacked PTEN by 23 per cent compared with abiraterone alone.

Around half of men with advanced prostate cancer have tumours with faulty PTEN genes, meaning they could potentially benefit from the combination treatment if it were to be approved.

That’s more than 10,000 men per year in the UK.

Men with tumours lacking PTEN tend to have a particularly poor prognosis, but the new phase III trial could open up the combination treatment as a new targeted approach to keep patients healthy for longer.

Among patients with tumours that lacked PTEN, 61 per cent of those who received the combination saw their tumour get smaller – compared with 39 per cent for those who took abiraterone on its own.

Additionally, 19 per cent of those taking the combination had a complete remission – meaning no sign of the disease was found – compared with 6 per cent for those taking abiraterone only.

The ipatasertib and abiraterone combination was also associated with greater and longer-lasting PSA response rates – used to monitor prostate cancer progression – in patients both with and without PTEN.

The drug combination works by simultaneously switching off two powerful growth signals that fuel prostate cancer. Abiraterone blocks signalling of the male hormone androgen receptor, while ipatasertib blocks another set of tumour growth signals involving the protein AKT.

Signals involving AKT are used by cancers that lack a functioning PTEN gene to grow and spread.

These cancers become ‘addicted’ to AKT signal and tend to be particularly aggressive and progress quickly.

The IPATential150 trial is the first to show that switching off the androgen receptor and AKT signalling provides a new treatment strategy that cuts off cancer’s evolutionary escape routes and stops the growth of aggressive cancers.

Confronting cancer’s ability to adapt and evolve is a key area of research at The Institute of Cancer Research (ICR) – a charity and research institute.

Study leader Professor Johann de Bono, Professor of Experimental Cancer Medicine at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, said:

“We have shown that combining an existing and a new drug to attack cancer on two different fronts can keep men with prostate cancer healthier for longer. The findings offer a promising new treatment option for patients with a common and aggressive type of prostate cancer, and could eventually change clinical practice for these men.

“PTEN is one of the most commonly deleted genes in prostate cancer, so this study offers hope to many patients.”

Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:

“The major challenge we face with cancer is its ability to evolve and become resistant to treatment. To overcome or prevent drug resistance, we are increasingly combining precision medicines so that we can attack patients’ cancers in several ways at once. This new study brings together abiraterone, a gold standard prostate cancer medicine which was discovered at the ICR, and a new experimental drug, in order to slow down cancer’s growth and progression. The combination could extend the time before men’s prostate cancer worsens, helping keep them healthy for longer so that they can spend as much time as possible with their loved ones.”

Peter Hartley, 68, from Market Harborough, has been receiving treatment at The Royal Marsden through the IPATential150 trial for three years, following his prostate cancer diagnosis.

Being on this research trial has seen Peter’s prostate specific antigen (PSA) levels drop rapidly, one of the key indicators of prostate cancer, reducing the size of his tumours and enabling him to keep living a healthy life. Peter said:

“When I was first diagnosed with advanced prostate cancer in June 2015 they told me there was nothing they could do and I would only have two to three years left, this was before I came to The Royal Marsden. Following a course of chemotherapy, I joined Professor De Bono’s research trial and for the past three years I’ve been given a new lease of life. Being on this trial has been nothing short of a miracle, I’ve had no side effects and my quality of life is fantastic.

“I feel so privileged and lucky to have this opportunity, to stay as healthy as possible for as long as possible. I’m monitored closely by my medical teams and have regular hospital checks which is reassuring. The nurses and doctors are amazing and can’t do enough for you. Thanks to the success of this treatment, I can continue doing the things I love like spending time with my wife, children and 3 grandchildren, visiting the Lake District and enjoying my golf, tennis and hiking!”

Source: The Institute of Cancer Research, London