Precision Oncology Makes a Difference in Bile Duct Cancer

ESMO 2019 Congress reported, in intrahepatic bile duct cancer patients with an FGFR alteration, that pemigatinib made a difference in a tumor type with few options: a 35% response rate and 21-month overall survival.

Management of biliary tract cancers, particularly cholangiocarcinoma, is changing rapidly with emerging precision drug strategies. Most research focuses on patients with alterations found in approximately 40% of intrahepatic cholangiocarcinomas: fibroblast growth factor receptor-2 (FGFR2) fusions and isocitrate dehydrogenase-1 (IDH1) mutations.

Presented at ESMO 2019, FIGHT-202 late-breaking abstract findings show clinically meaningful activity of pemigatinib in previously treated advanced cholangiocarcinoma (Abstract LBA40).

Pemigatinib is an FGFR inhibitor, and responses in this study were limited to patients with FGFR2 rearrangements or fusions.

Study Results

• The objective response rate, including 3 complete responses and a median response duration of 7,5 months, was 35,5% .
• The disease control rate was 82%.
• Median progression-free and overall survival were 6.9 and 21.1 months, respectively.
• The most common side effect was mild (grade 1-2) hyperphosphatemia (frequency 60%), meaning elevated blood phosphate, primarily controllable through dietary modification and phosphate binders.

Several FGFR-targeting drugs are being developed in biliary tract cancers. In a noncomparative phase IIa study, another FGFR2 inhibitor, derazantinib , also showed clinical activity (Abstract 721P). Similar to FIGHT-202 findings, activity was more pronounced with FGFR2 aberrations: an objective response rate of 21%.

Patients with FGFR2 fusions appear to have a significant survival advantage over those without FGFR fusions. New research suggests younger age (<65), alcohol abuse and hepatitis B or C positivity increase the likelihood of FGFR2 fusions (Abstract 723P).

Genetic Analysis of Tumors Will Become a New Standard for Patients Diagnosed with Advanced Cholangiocarcinoma

Meaningful advances include investigation of new first-line agents. For example, the ongoing PROOF study compares the pan-FGFR inhibitor infigratinibin advanced / metastatic or inoperable cholangiocarcinoma with the standard treatment, gemcitabine plus cisplatin (Abstract 832TiP).

These results, first reported at ESMO 2019, show that better understanding the genomic basis of cholangiocarcinoma leads to targeted treatments with great promise in trials, but only when given to the right patients. Precision medicinehas demonstrated efficacy for years in lung cancer and other oncology fields, but should now also be considered in cancers with limited options, such as cholangiocarcinoma.