A gene test could guide decisions around chemotherapy for bowel cancer

pharmafile | March 3, 2023 | News story | Medical Communications  

Scientists from the Institute of Cancer Research London, Imperial College London and the Netherlands Cancer Institute have researched a gene test which can select which advanced bowel cancer patients will respond the best to chemotherapy.


Their findings, published in Nature Medicine, describe how patients without mutations in the KRAS gene (wildtype) may benefit from trifluridine/tipiracil chemotherapy: a last-line treatment for patients whose cancer has not responded to anything else.


The researchers profiled the entire genomes of 37 patients with advanced bowel cancer who had been treated with trifluridine/tipiracil, finding that a specific mutation in the KRAS gene called KRASG12 was linked to poor survival in treated patients. This was confirmed by data from a further 960 patients from 36 centres across the UK.


Next, clinical data from the RECOURSE study was looked at to ascertain the impact of treatment on survival for patients with different KRAS mutations. They found that patients with a KRASG13 mutation ‒ 8% of those in the trial ‒ saw their median survival triple from 2.9 months without treatment to 8.7 months with the treatment. Comparatively, patients with the KRASG12 mutation had no benefit from treatment ‒ both those who received a placebo and those who received the treatment survived for an average of six months.


Overall, the findings suggest that patients with KRASG12 ‒ which is around 28% of all bowel cancer patients ‒ do not benefit from trifluridine/tipiracil chemotherapy.


The gene test is already used by the NHS for advanced bowel cancer patients to look for KRAS mutations in their cancer, to inform if they would benefit from cetuximab. Based on the evidence from the findings, NHS doctors can begin to apply the same test for trifluridine/tipiracil.


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.”


James Spargo

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