New therapy for bile duct cancer extends patients’ lives

A new personalised cancer treatment can radically improve the outlook for some patients with bile duct cancer, a new study involving UCL researchers has found.

The clinical trial – the European arm of which was led by UCL researchers – found that patients who were otherwise facing end of life care survived for up to two years when treated with the drug futibatinib. The results are published in the New England Journal of Medicine.

The drug targets a particular genetic alteration found in around 14% of bile duct cancers, called FGFR2 fusions. Around 300 patients a year in the UK are diagnosed with bile duct cancer with this genetic alteration.

There are very few treatment options for bile duct cancer and the survival is poor, with patients newly surviving on average for just 12 months. Although the cancer is uncommon, incidence is on the rise globally.

This international trial recruited 103 patients with bile duct cancer who had undergone at least one chemotherapy treatment, but whose cancer had become resistant. The patients’ cancer tumours had been genetically analysed to check that they had an alteration in a particular group of genes, known as fibroblast growth factor receptors (FGFR). The drug, futibatinib, is known as an FGFR-2 inhibitor, as it targets this genetic alteration.

When the patients were treated with futibatinib, the results were striking. The drug was more effective at reducing the size of the tumour, with the cancer shrinking by over 40%, compared to 25% with chemotherapy. The drug also produced modest side effects compared to chemotherapy.

Patients on treatment survived for up to two years, even though they had advanced cancer and had sometimes tried up to five other treatments before entering the trial.

European lead and senior author on the paper, Professor John Bridgewater (UCL Cancer Institute and University College Hospitals NHS Foundation Trust) said: “This is a gamechanger, which turns treatment for this group of patients on its head. Instead of treating them with the blunderbuss that is chemotherapy, which attacks healthy cells alongside the cancer, we can offer a truly personalised treatment that just targets a specific alteration within the cancer”.

“The benefits that patients saw in the trial were remarkable. It’s absolutely essential that patients with bile duct cancer get their cancer tested to find out if they have this abnormality. We can’t afford to miss one of these alterations: the difference they could make to treatment outcomes is dramatic.”

There are currently other FGFR inhibitors already in clinical use, including one called pemigatinib, which has been approved for use in the UK by the National Institute for Care and Health Excellence (NICE). However, existing FGFR inhibitors are known to be susceptible to resistance within the cancer. Laboratory tests have shown this is less likely to be a problem with futibatinib, as it targets the FGFR abnormality in a more specific way, and so is likely to be more effective than existing drugs.

Trials are already underway looking at the possibility of using futibatinib as a first line treatment in place of chemotherapy. Professor Bridgewater said: “The question these trials now need to answer is not whether patients should be getting this treatment, but when.

“Hopefully, this kind of genetically driven treatment will become the new normal for oncology. Personalised treatment has long been a buzz word in cancer, but this trial is the real thing – proving that it can be done and bring huge benefits to specific groups of patients.”