By james art 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 positive hormone receptor (HR+) negative human epidermal growth factor 2 (HER2-) breast cancer.
The study, known as INAVO120 and published in The New England Journal of Medicine, included 325 patients from 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, about 161 patients were given the three-drug combination, which consists of 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, received placebo plus palbociclib and fulvestrant.
The researchers found that the three-drug therapy slowed 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 showed no signs of disease progression, compared with 21.1% of placebo patients.
Lead author Nick Turner, 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 therapeutic combination that 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 first-line treatment for the disease.”
“This is a huge breakthrough, which builds on a long research program 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 and almost 11,500 deaths each year.
About 70% of patients are estimated to have HR+/HER2- breast cancer, while PIK3CA mutations are found in 35%-40% of HR+ breast cancers.
The combination of palbociclib and fulvestrant is available as an option for patients with certain types of breast cancer on the NHS from 2022.
The three-drug therapy inavolisib, palbociclib and fulvestrant is not approved in the UK but was given the green light by the US Food and Drug Administration (FDA) earlier this month.
Prof Turner added: “This new combination helps prevent cancer becoming resistant to therapy and leads to more frequent long-term responses.
“We look forward to seeing this treatment option licensed and becoming the standard of care as quickly as possible.”
Professor Christian Hellin, Chief Executive of the Institute of Cancer Research London, said: “To achieve further improvements in cancer survival, we need to find new ways to overcome drug resistance.
“By developing drugs with different mechanisms of action, we can block cancer’s escape routes and give people living with metastatic breast cancer a chance to live well for longer.”
“One challenge with combination therapies is finding the right doses for drugs and disentangling their individual effects.
“It is very encouraging to see that this study has shown that inavolisib-based therapy is not only very effective when taken together, but the therapy is generally well tolerated by patients.”
Ann Lurie, 53, received 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: “After 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 was given the targeted therapy drug palbociclib.
“After three years the treatment stopped working for me, but luckily I was able to get inavolisib as part of a clinical trial.
“Apart from fatigue, I have had minimal side effects and although I am now on a different treatment, I would not be here if I had not had the opportunity to join the trial at the Royal Marsden.”
Dr Simon Vincent, director of research, support and advocacy at the charity Breast Cancer Now, said: “It is estimated that around 61,000 are living with secondary breast cancer in the UK which, although currently incurable, can be treated to slow the spread of disease and improve quality of life.
“These findings show that this new treatment approach, using a combination of three drugs, can give people living with secondary breast cancer an extra eight months without their disease getting worse, giving them valuable more time with their close ones.’