New drug combination attacks prostate cancer on two fronts to keep men healthy for longer

08 July 2021

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 has shown.

Study leader Professor Johann de Bono
Study leader Professor Johann de Bono

Published in The Lancet today, results from the IPATential150 study showed that 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 Royal Marsden and The Institute of Cancer Research, London, 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 these latest findings provide the first strong evidence of the benefit of combining the two drugs.

The international phase III trial 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.

Results 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. 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.

PTEN is one of the most commonly deleted genes in prostate cancer, so this study offers hope to many patients. - Professor Johann de Bono”

Around half of men with advanced prostate cancer have tumours with faulty PTEN genes and this group of patients tend to have a particularly poor prognosis. This new phase III trial could open up the combination treatment as a new targeted approach to keep these patients healthy for longer, potentially benefitting more than 10,000 men per year in the UK.

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.

Study leader Professor Johann de Bono, Consultant Medical Oncologist at The Royal Marsden and Professor of Experimental Cancer Medicine at The Institute of Cancer Research, London, 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.”

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, 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!”

The IPATential150 trial was funded by Roche.