A trial using a blood test to find certain gene changes and decide treatment for advanced breast cancer (plasmaMATCH)

Cancer type:

Breast cancer
Secondary cancers

Status:

Results

Phase:

Phase 2

This trial looked at different treatment options for women with certain gene changes (mutations) Open a glossary item. It was for women who had breast cancer that had:

  • come back (recurrent or locally advanced breast cancer) or
  • spread to another part of the body (secondary or metastatic breast cancer)

The trial was supported by Cancer Research UK. It was open for people to join between 2016 and 2020. The team published results in 2020 and 2023.

More about this trial

When this trial was done, doctors took samples of cancer cells (biopsies) to look for genetic changes (mutations). They use the results to help decide which treatment is best for each person.

Cancer cells can have different genetic changes over time. It isn’t always possible to take repeat biopsies from someone with advanced cancer. So researchers want to find other ways to look for these changes.

One way is to look at the circulating tumour DNA (ctDNA) Open a glossary item in blood samples. ctDNA is tiny bits of genetic material (DNA) from cancer cells that get into the bloodstream.

In this trial, researchers compared DNA changes in biopsy results and blood samples. They wanted to find out how accurate ctDNA testing is.

They also wanted to see if they can pick the best treatment, depending on people’s genetic changes.

The people taking part were put into a treatment group depending on the genetic changes the research team found.

The main aims of the trial were to find out:

  • if ctDNA results are as good as biopsy results
  • how well the different treatments work for people with changes in ctDNA

Summary of results

This trial showed that ctDNA  Open a glossary item analysis is an accurate way to look for genetic changes in breast cancer.

Trial design
People with changes in their ctDNA were put into 1 of 5 treatment groups. The group they were in depended on the type of breast cancer and the genetic changes they had.

Group A was for people with an ESR1 gene mutation. They had a hormone therapy called fulvestrant. They had this more often than usual.

Group B was for people with a HER2 gene mutation. Those with oestrogen receptor positive Open a glossary item cancer had fulvestrant and a targeted treatment called neratinib. Those with oestrogen receptor negative Open a glossary item cancer had neratinib alone.

Group C was for people with an AKT1 gene mutation. They had fulvestrant and a targeted treatment called capivasertib (AZD5363).

Group D was for people with an AKT or PTEN gene mutation. They had capivasertib alone.

Group E was for people who didn’t have any gene mutations and had triple negative breast cancer. This means their cancer doesn’t have oestrogen, progesterone or HER2 receptors. They had two targeted treatments called olaparib and ceralasertib.

Results
The trial team looked for genetic changes in ctDNA of more than 1,000 people:

  • 84 people with an ESR1 gene mutation joined group A
  • 21 people with a HER2 gene mutation joined group B
  • 18 people with an AKT1 gene mutation joined group C
  • 19 people with an AKT or PTEN gene mutation joined group D

A total of 75 people with triple negative breast cancer joined group E:

  • 60 who didn’t have any genetic changes in their ctDNA
  • 15 who had genetic changes but weren’t able to join any of other treatment groups at the time

The people taking part had had treatment already, but their cancer had come back or started to grow again.

The team looked at how similar the results were for two different ways of measuring ctDNA. They found the two tests identified the same mutations for between 96% and 99% of samples, depending on the gene.

The results also showed that the gene changes in the ctDNA in the blood samples were very similar to those in the cancer cells (tissue biopsies). The changes were the same for between 98% and 100% of samples when they were taken within 2 months of each other.

How well treatment worked
Researchers were able to analyse how the treatment was working for most of the people who took part.

They found that the cancer responded to treatment in:

  • 6 out of 74 people (8%) in group A
  • 5 out of 20 people (25%) in group B
  • 4 out of 18 people (22%) in group C
  • 2 out of 19 people (11%) in group D
  • 12 out of 70 people (17%) in group E

Conclusion
The team’s overall conclusion was that genetic changes found in ctDNA are very similar to those in cancer cells. And that using blood samples to test for genetic changes in people with breast cancer was accurate, and easier than taking biopsies.

They made the following conclusions for the different groups.

Group A – having fulvestrant more often may not be a useful treatment for people with an ESR1 gene mutation.

Group A - fulvestrant may work better for certain sub types of ESR1 changes.

Group B - neratinib, with or without fulvestrant, may be a useful treatment for people with HER2 changes.

Group C - capivasertib and fulvestrant may be a useful treatment for people who have oestrogen receptor (ER) positive cancer and AKT1 changes.

Group D - capivasertib alone may not be a useful treatment for people with PTEN gene mutations.

Group D - capivasertib alone seemed to work better for people with certain AKT1 gene mutations.

Group E – olaparib and ceralasertib doesn’t seem to be useful for people with triple negative breast cancer and no mutations.

Group E - olaparib and ceralasertib may be useful for people with specific biomarkers Open a glossary item, but more work needs to be done.

More detailed information
There is more information about this research in the references below.

Please note, the information we link to here is not in plain English. It has been written for healthcare professionals and researchers.

Circulating tumour DNA analysis to direct therapy in advanced breast cancer (plasmaMATCH): a multicentre, multicohort, phase 2a, platform trial
N Turner and others
The Lancet Oncology, 2020. Volume 21, issue 10, pages 1296 – 1308.

Olaparib and Ceralasertib (AZD6738) in Patients with Triple-Negative Advanced Breast Cancer: Results from Cohort E of the plasmaMATCH Trial (CRUK/15/010)
A Ring and others
Clinical Cancer Research, 2023. Volume 29, issue 23, pages 4751 - 4759.

Where this information comes from
We have based this summary on the information in the article above. This has been reviewed by independent specialists (peer reviewed Open a glossary item) and published in a medical journal. We have not analysed the data ourselves. As far as we are aware, the links we list above are active and the articles are free and available to view.

Recruitment start:

Recruitment end:

How to join a clinical trial

Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Professor Nicholas Turner

Supported by

Cancer Research UK
ICR Clinical Trials and Statistics Unit
Stand Up to Cancer
The Institute of Cancer Research
The Royal Marsden NHS Foundation Trust
AstraZeneca
Puma Biotechnology

Other information

There is more information about this trial on the plasmaMATCH website.

If you have questions about the trial please contact our cancer information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

13382

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

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