A gene test already used routinely by the NHS could help guide the use of chemotherapy in bowel cancer patients, according to a new study published in Nature Medicine.
Patients with late-stage bowel cancer receive a series of chemotherapies and targeted medicines, but the disease eventually adapts and becomes resistant to each treatment.
Trifluridine/tipiracil chemotherapy, taken as tablets, is a last-line treatment available on the NHS for patients who have exhausted most other therapies. However, responses vary greatly between patients, with some showing good, long-term responses, and others seeing no benefits.
The gene test assessed in the study, which is already used to predict patients’ responses to other targeted cancer drugs, could allow doctors to select those whose cancers are likely to be sensitive to chemotherapy, and spare those who will not respond from unnecessary side effects.
The team, made up of researchers from the Institute of Cancer Research (ICR), Imperial College London and the Netherlands Cancer Institute, are calling for regulators to rapidly incorporate the findings into guidelines so that using the test to direct treatment with trifluridine/tipiracil becomes the standard of care.
Professor Kristian Helin, chief executive of the ICR, said: “Treating cancer well is not just about allowing people to live for longer, but also about giving them the best possible quality of life.
“Although chemotherapy can be very effective for many patients, it can also have debilitating side effects, so it is important to have as much information as possible about how likely treatment is to work.”
During the study, the team profiled the entire genomes of 37 patients with advanced bowel cancer who had been treated with trifluridine/tipiracil, and found that a specific mutation in the KRAS gene called KRASG12 was linked to poor survival. This was then confirmed from a further 960 patients across the UK.
Separate data from a clinical trial showed that patients with another mutation in the KRAS gene called KRASG13 – 8% of those in the study – saw their median survival triple with the treatment.
For those without KRAS mutations, survival was found to improve by around two months in patients treated with trifluridine/tipiracil compared to placebo.
Professor Nicola Valeri, honorary professor of gastrointestinal oncology at the ICR and Imperial College, 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.”