A clinical trial, co-led by one of our researchers, has shown that a new drug for secondary breast cancer can be used to treat emerging resistance to treatment - months before tumours have a chance to grow.
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The SERENA-6 trial found that the new drug camizestrant in combination with CDK4/6 inhibitors cut the risk of the disease getting worse by 56% for people with advanced hormone receptor (HR) positive, HER2-negative breast cancer.
It’s also the first global study to show that using blood tests that can detect emerging resistance to guide breast cancer treatment has a clinical benefit.
Scientists hope these findings could lead to a new treatment strategy for some people with secondary breast cancer.
Targeting hormone therapy resistance
For people with HR-positive, HER2-negative secondary breast cancer, initial treatment is often a targeted drug called a CDK4/6 inhibitor plus a type of hormone treatment known as an aromatase inhibitor.
While taking this treatment, some people develop changes to the ESR1 gene which allows the cancer to grow and resist hormone treatments. When this happens, chemotherapy can be an option, but delaying this is important because of the side effects it comes with.
Camizestrant, which was discovered and developed by AstraZeneca, is a type of hormone therapy drug described as a ‘next-generation’ selective oestrogen receptor degrader (SERD). This drug not only prevents oestrogen from attaching to cancer cells but also destroys the receptors themselves, making it harder for the cancer to resist treatment.
The SERENA-6 trial, co-led by researchers at The Institute of Cancer Research, London, The Royal Marsden NHS Foundation Trust and Institut Curie, Paris, tested whether switching from an aromatase inhibitor to camizestrant to treat emerging ESR1 changes could stop the cancer growing for longer, and delay chemotherapy.
Understanding the clinical trial
Researchers screened 3,325 people from 23 countries with HR-positive, HER2-negative secondary breast cancer and found that 548 had ERS1 changes. For this, they used a blood test, also called a liquid biopsy, that can analyse small amounts of circulating tumour DNA in the blood (ctDNA).
Then, half of the people with ERS1 changes were given camizestrant alongside their CDK4/6 inhibitor drug instead of their aromatase inhibitor drug. The other half continued taking an aromatase inhibitor.
The results showed that the camizestrant combination reduced the risk of breast cancer progression by over half (56%). The researchers also found that the average progression free survival time for people taking this treatment combination was 16 months, compared with 9.2 months for the control group.
The camizestrant combination was generally well tolerated with only a few people (1%) experiencing side effects that led them to discontinue the treatment. And, the researchers found this therapy reduced the risk of someone’s general health and quality of life getting worse by 47%.
This is a pivotal moment in breast cancer care. These results demonstrate that using liquid biopsy blood tests to spot emerging resistance in tumours, before they start to grow and make the patient unwell, can guide early intervention with camizestrant to delay disease progression in patients with ESR1 mutations. This proactive approach not only extends the benefit of first line therapy but also redefines how we think about drug resistance in this type of breast cancer. This is a potential new treatment strategy in oncology to treat developing resistance before it causes disease progression.
Professor Nicholas Turner
Co-principal investigator
This study was published in The New England Journal of Medicine and funded by AstraZeneca. The Breast Cancer Clinical Trials Team that co-led the SERENA-6 trial are based in the Ralph Lauren Research Wing, Kuok Research Centre within the Oak Cancer Centre, which was funded by The Royal Marsden Cancer Charity.
Pioneering research into liquid biopsies
Professor Nicholas Turner and his team at the Breast Cancer Now Research Centre at the Institute of Cancer Research, London, have been pioneering research into the use of liquid biopsy blood tests to detect breast cancer relapse and guide treatment for more than a decade.