Gene test could predict bowel cancer therapy success

A gene test already used by the NHS could help to predict if late-stage bowel cancer patients will benefit from chemotherapy.

Scientists hope their findings, published in Nature Medicine, will mean the introduction of the first routine use of a genetic test to predict how bowel cancer patients will respond to trifluridine/tipiracil (FTD/TPI), a last-line treatment for individuals who have exhausted most other therapies.

The gene test is already used as part of standard of care in the UK and worldwide to predict patients’ responses to other targeted cancer drugs.

The study, by teams at The Institute of Cancer Research, London, Imperial College London and the Netherlands Cancer Institute, looked at data from three sources to understand if genetic markers could help to explain the differences in survival of patients because responses to the two drugs greatly varies.

They first profiled the entire genomes of 37 patients with advanced bowel cancer, who had been treated with FTD/TPI, and found the KRASG12 mutation in the KRAS gene was linked to poor survival in treated patients. This was confirmed in data from a further 960 patients from 36 centres across the UK.

They went on to examine data from the RECOURSE clinical trial and identified that individuals with the KRASG13 mutation in the KRAS gene – 8% of those on the trial – saw their median survival triple from 2.9 months without treatment to 8.7 months with the treatment.

This was compared to no benefit from treatment in patients with KRASG12 mutations. Patients who received placebo and those who received the treatment survived for an average of six months.

Patients without mutations in KRAS saw their survival rate improve by about two months if they were treated with FTD/TPI compared to placebo.

The findings suggested that patients with KRASG12 mutations, which accounted for about 28% of all patients with bowel cancer, do not benefit from FTD/TPI, so should avoid the therapy.

However, patients without mutations in KRAS may benefit from FTD/TPI, while those with a KRASG13 mutation are likely to do very well on the treatment.

Professor Nicola Valeri, honorary professor of gastrointestinal oncology at The Institute of Cancer Research and Imperial College, London, said: “This is the first time we have a genomic marker already used in the clinic that can tell us whether a patient’s cancer will be sensitive or resistant to chemotherapy. We hope doctors will use this data to improve care for patients with advanced bowel cancer without delay.

“It will be difficult for some patients to find out that this last-line drug will not benefit them, but this test will mean they are able to avoid unnecessary side effects and have a better quality of life with advanced cancer. Fortunately, our findings also reveal a group of patients who see substantial benefits from taking this type of chemotherapy.”

Van der Haar J, Ma X, Ooft SN et al. Codon-specific KRAS mutations predict survival benefit of trifluridine/tipiracil in metastatic colorectal cancer. Nature Medicine 2 March 2023.


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