A clinical trial, led by one of our scientists, has revealed the benefits of a powerful combination of 3 drugs for aggressive secondary breast cancer.
This ‘triplet therapy’ doubled the length of time before the cancer progresses, compared to a targeted treatment currently on the NHS.
The team, based at The Institute of Cancer Research, London and The Royal Marsden NHS Foundation Trust, hope the results will lead to the licencing of a new drug called inavolisib. And that this triplet therapy becomes the standard of care for some people with secondary breast cancer.
Understanding the clinical trial
The INAVO120 study was testing a combination of 3 drugs to treat hormone receptor (HR) positive, HER2-negative secondary breast cancer with an altered PIK3CA gene.
This phase III clinical trial, funded by Roche, involved 325 people from 28 countries. In more than 50% of people, their cancer had already spread to 3 or more organs and most had already had chemotherapy.
The triplet therapy consisted of:
- Palbociclib, a CDK4/6 inhibitor drug
- Fulvestrant, a hormone therapy drug
- Inavolisib, a new PI3K inhibitor drug
Results showed that the new triplet therapy was able to delay the disease by an average of 15 months. In comparison, a control group given palbociclib and fulvestrant saw disease progression halted for an average of 7.3 months.
After 18 months, 46.2 % of people in the triplet therapy group were still showing no signs of disease progression. But in the control group, just 21.1% saw these benefits over the same period.
The triplet therapy was generally well tolerated, with only a few patients experiencing side effects that caused them to stop the treatment.
The science behind the ‘triplet therapy’
Palbociclib and fulvestrant are 2 drugs which are offered together for treating HR-positive, HER2-negative breast cancer that’s spread. They’ve been an approved treatment of breast cancer on the NHS since September 2022.
Around 70% of breast cancers are HR-positive and HER2-negative. Altered PIK3CA genes are found in 35-40% of HR-positive breast cancers. They’re also linked to tumour growth, disease progression, and treatment resistance.
Inavolisib, a new drug, works by blocking the activity of the PIK3CA protein. It also has a second mode of action which triggers the PIK3CA protein to break down, destroying it altogether. This process is known as targeted protein degradation.
The results of this study showed substantial shrinking, or response, in cancer growth in around 58.4% of people in the triplet therapy group compared to 25% in the control group.
This led the United States Food and Drug Administration (FDA) to grant special ‘breakthrough therapy’ status for inavolisib, with full approval expected later this year.
The impact of this study
The team, led by Professor Nicholas Turner at the Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research (ICR), now hopes the results will lead to the licensing of inavolisib. And that this the triplet therapy will become the standard of care in people with this form of the disease.
This is the first study to demonstrate the potential of triplet therapy, 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.
Professor Nicholas Turner
Building on decades of science
This breakthrough follows a pioneering programme of discoveries made at our research centre going back over a decade.
In 2015, the PALOMA3 trial showed that palbociclib and hormone therapy together delayed disease for an average of 9 months, compared with fewer than 4 months with hormone therapy alone.
Then in 2016, our researchers published research which showed how breast cancer cells can become resistant to CDK4/6 inhibitors like palbociclib. They found that a combination of 3 drugs would provide the best tumour control compared with 2-drug combinations.
4 years later, a study trialled a combination of palbociclib, hormone therapy, and a PI3K inhibitor called taselisib. The researchers found that taselisib was not quite the right PI3K inhibitor. But, this study was an important proof of concept for triplet therapy and paved the way for the INAVO120 study.
Professor Nicholas Turner added:
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. This triplet therapy helps prevent the cancer becoming resistant to therapy, and results in much 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 Nicholas Turner
The study was funded by Roche and published in New England Journal of Medicine.
Our research into secondary breast cancer
Professor Nick Turner is just one of many scientists we fund hoping to improve life for people with secondary breast cancer. Find out more about our work into secondary breast cancer research.