Bile duct cancer, which comprises cholangiocarcinoma and gall bladder cancer, is a rare but aggressive disease in which malignant cancer cells form in the bile ducts -- a network of tubes connecting the liver, gallbladder, and small intestine. Treatment options are few and survival rates poor, with patients surviving about a year. Although uncommon, bile duct cancer's incidence is on the rise globally.

This international trial, set across 13 countries and sponsored by Taiho Oncology, recruited 103 patients with bile duct cancer who had undergone at least one chemotherapy treatment and whose cancers had become resistant. The patients' tumors had been genetically analyzed to check for an alteration called FGFR2 fusion in a particular group of genes known as fibroblast growth factor receptors (FGFR). The drug futibatinib, an FGFR-2 inhibitor, targets this genetic alteration, found in around 14% of bile duct cancers.

When treated with oral futibatinib tablets, the results were striking. The drug effectively reduced tumor sizes, shrinking patient cancers by over 40%, compared to 25% with chemotherapy. The drug also had fewer side effects than chemotherapy, improving the quality of life for these patients. Despite their advanced cancers, patients survived up to two years. Trial data led to the U.S. Food and Drug Administration (FDA) to approve futibatinib, although the U.K. has yet to do so. Trials investigating the use of FGFR2 inhibitors as a first-line treatment replacing chemotherapy are underway.

Other FGFR inhibitors currently in clinical use include pemigatinib, which is approved for use in the U.K. However, these FGFR inhibitors are susceptible to resistance within the cancer. The researchers contend that this problem is less likely with futibatinib, as it targets the FGFR abnormality in a more specific way. They emphasize the necessity of doctors putting their cholangiocarcinoma patients forward for molecular testing.

"These results turn 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 personalized treatment that just targets a specific alteration within the cancer," said UCL Cancer Institute senior author John Bridgewater, PhD, in a statement. "It's important that patients with bile duct cancer get their cancer tested to find out if they have this abnormality. The question these trials now need to answer is not whether these patients should be getting this treatment, but when."