Dr Liao on the Value of Molecular Testing in Biliary Tract Carcinoma

Chih-Yi Liao, MD, associate director, Gastrointestinal Oncology; co-director, Neuroendocrine Tumor Program; assistant professor of medicine, UChicago Medicine, discusses the value of molecular testing in biliary tract carcinoma.

Molecular testing is essential for patients with biliary tract carcinoma, especially as more targeted therapies are being integrated into clinical practice, Liao explains.

Data from the phase 2 FIGHT-202 study (NCT02924376) showed that at a median follow-up of 15 months, pemigatinib (Pemazyre) generated an objective response rate (ORR) of 36% with a median duration of response of 7.5 months in patients with locally advanced or metastatic cholangiocarcinoma harboring FGFR2 fusions or rearrangements. These data supported the FDA approval of pemigatinib for the treatment of patients with previously treated, locally advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements, as detected by an FDA-approved test, in April 2020.

Additionally, data from phase 1/2 single arm open label FOENIX-CCA2 trial (NCT02052778) supported the FDA's accelerated approval of futibatinib (Lytgobi) for previously treated adult patients with unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 fusions.

Although many of these targeted therapies are currently used in the second-line setting or beyond, ongoing trials such as the phase 3 randomized FIGHT-302 trial (NCT03656536)comparing pemigatinib to gemcitabine plus cisplatin are investigating targeted therapies as first-line treatment for patients with advanced biliary tract cancer. Consequently, Liao emphasizes the importance of obtaining molecular testing results early in the treatment course to aid in future treatment planning and identifying potential clinical trials for patients.

Liao advocates for conducting molecular testing at the time of diagnosis, even if it does not immediately influence the first-line treatment decision. This early testing approach ensures that clinicians are prepared for subsequent treatment options as the disease progresses. Typically, Liao orders both tissue-based next-generation sequencing (NGS) and liquid biopsy tests.

Although tissue-based NGS is more sensitive, Liao says obtaining sufficient tissue for testing can be a significant challenge in patients with biliary tract cancer, particularly in those with intrahepatic cholangiocarcinoma. In such cases, liquid biopsy serves as a valuable alternative; however, its sensitivity is generally lower than that of tissue-based assays, Liao notes.

One advantage of liquid biopsy is its faster turnaround time, allowing clinicians to make timely and informed treatment decisions. However, Liao concludes by noting the importance of using both tissue-based and liquid biopsy testing, when possible, to ensure comprehensive molecular profiling.