Bile duct cancer (cholangiocarcinoma) is a rare aggressive disease that begins in the bile ducts. It is usually found at an advanced stage and up to two thirds of patients who have surgery experience disease recurrence.
Rearrangements or fusions of the Fibroblast Growth Factor Receptor (FGFR) 2 gene have been found in up to 14% of bile duct cancer patients with a subtype in the liver called intrahepatic cholangiocarcinoma (iCCA). These alterations transform FGFR2 into an oncogene that drives the growth of cancer - giving rise to ‘oncogene-addicted tumors’.
Oncogene-addiction refers to a biological process where tumor cells are heavily relying on one or just a few deregulated or mutated genes for growth. This dependence is considered a ‘cancer-weakness’ that can be exploited in personalized therapies by blocking the pro-growth signal from these critical oncogenes, thus preventing the survival of the cancerous cells.
Recently, promising new treatments have been developed that inhibit the FGFR protein family. Already, two selective FGFR inhibitors - pemigatinib and infigratinib - have received FDA approval, with selected patient responses reported to be 35.5% and 23.1%, respectively.
Published in the prestigious New England Journal of Medicine, an international team of researchers including Dr. Heinz-Josef Klümpen from Cancer Center Amsterdam now report results of a Phase II trial (FOENIX-CCA2) with a new FGFR inhibitor, futibatinib.
The patient response to futibatinib was 42%, which is higher than the previous inhibitors. The use of futibatinib also resulted in durable responses, stable quality of life during the 9-month treatment, and higher survival than standard chemotherapy. Additionally futibatinib has a more favorable toxicity profile, and the frequency of complete hair loss occurred in only 8% of patients compared to 46% in the pemigatinib study.
The authors called for improvements in the DNA profiling of tumor tissue-biopsy to better identify patients who can benefit from these targeted treatments. “A practical, high-performance method for identifying patients that have these therapeutic targets will significantly contribute to improving their care,” says Dr. Klümpen.
“Data from this study establish futibatinib as having measurable clinical benefit for patients with this disease and show the value of molecular profiling to identify tumors that are likely to respond to FGFR2 inhibition,” the authors conclude.
Currently, a phase III trial is ongoing to assess overall survival following futibatinib therapy in first line. In addition, other studies are comparing FGFR-inhibition to standard chemotherapy as a first line treatment. Considering the rarity of this subtype of bile duct cancer, it is still unclear when these ongoing clinical trials will conclude.
For more information, read the report, watch the video, or contact Dr. Heinz-Josef Klümpen.
This article was created for Cancer Center Amsterdam.
© 2023 NHBC– All rights reserved.