A three-drug combination targeting aggressive advanced breast cancer could potentially double the amount of time patients live without the disease progressing, a trial has found.
Researchers hailed the “huge breakthrough” as potentially “transformative” for those with a common form of breast cancer.
A mutation in the gene known as PIK3CA causes cells to divide and replicate uncontrollably, leading to the development of PIK3CA-mutated hormone receptor positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) breast cancer.
The study, known as INAVO120 and published in the The New England Journal of Medicine, included 325 patients from across 28 countries.
More than half had cancer that had spread to three or more organs, while more than 80% had already had chemotherapy.
Of the total, some 161 patients were given the three-drug combination, which comprised two targeted drugs – palbociclib, a type of cancer growth blocker, and a new drug called inavolisib, which blocks the activity of the PI3K protein – as well as the hormone therapy fulvestrant.
The placebo group, which included 164 patients, were given a placebo plus palbociclib and fulvestrant.
Researchers found the three-drug therapy delayed disease progression by an average of 15 months compared with 7.3 months in the placebo group.
After 18 months, 46.2% of patients in the three-drug group were showing no signs of disease progression compared with 21.1% of placebo patients.
Lead author Nick Turner, a professor of molecular oncology at the Institute of Cancer Research, London, and consultant medical oncologist at the Royal Marsden NHS Foundation Trust, said: “This is the first study to demonstrate the potential of a therapy combination, which targets the three key aspects of the biology of PIK3CA mutant HR-positive breast cancer.
“The results show that inavolisib in combination with palbociclib and fulvestrant significantly improves progression-free survival when given as a first treatment for the disease.
“It is a huge breakthrough that builds on a long programme of research at the ICR which could represent a transformative advance for people with this type of breast cancer.”
According to Cancer Research UK there are more than 56,000 new cases of breast cancer every year and almost 11,500 deaths.
It is understood about 70% of patients have HR+/HER2- breast cancer, while PIK3CA mutations are found in 35%-40% of HR+ breast cancers.
The combination of palbociclib and fulvestrant has been available as an option for patients with certain types of breast cancer on the NHS since 2022.
The three-drug therapy of inavolisib, palbociclib and fulvestrant is not approved in the UK, but was given the green light by the USA’s Food and Drug Administration (FDA) earlier this month.
Prof Turner added: “This new combination helps prevent the cancer becoming resistant to therapy, and results in more frequent long-term responses.
“We look forward to seeing this treatment option being licensed and becoming the standard of care as quickly as possible.”
Professor Kristian Helin, chief executive of the Institute of Cancer Research, London, said: “To drive further improvements in cancer survival, we must find new ways of overcoming resistance to drug treatments.
“By developing medicines with different mechanisms of action, we can block off cancer’s escape routes and give people living with metastatic breast cancer the chance to live well for longer.
“One challenge with combination therapies is finding the right dosages for drugs and untangling their individual effects.
“It is very encouraging to see that this study showed that the inavolisib-based therapy is not only very effective when taken together but the therapy generally was well-tolerated by patients.”
Anne Lury, 53, was given inavolisib after joining a clinical trial at the Royal Marsden.
She was diagnosed with stage two breast cancer in 2007 and 10 years later was told the disease had spread to other parts of her body.
Ms Lury said: “Following my diagnosis, I was treated with surgery, chemotherapy and radiotherapy, and when the cancer spread to other parts of my body 10 years later I received the targeted therapy drug palbociclib.
“After three years, the treatment stopped working for me, but, thankfully, I was able to receive inavolisib as part of a clinical trial.
“Aside from fatigue I had minimal side-effects, and although I’m now on other treatment I wouldn’t be here if I hadn’t had the opportunity to join the trial at the Royal Marsden.”
Dr Simon Vincent, director of research, support and influencing at the charity Breast Cancer Now, said: “Around 61,000 are thought to be living with secondary breast cancer in the UK which, although currently incurable, can be treated to slow the spread of the disease and improve quality of life.
“These findings show that this new treatment approach, using a combination of three drugs, could provide people living with secondary breast cancer an additional eight months without their disease getting worse, giving them precious more time with their loved ones.”
