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 

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 

 fusions or rearrangements, as detected by an FDA-approved test, in April 2020.

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

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.

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Chih-Yi Liao, MD, discusses the value of molecular testing in biliary tract carcinoma.

Chih-Yi Liao, MD, discusses key considerations for the selection of single-agent vs combination regimens in frontline metastatic hepatocellular carcinoma.

Dr Liao on Selecting Between First-Line Monotherapy and Combination Approaches in HCC

Chih-Yi Liao, MD, associate director, Gastrointestinal Oncology; co-director, Neuroendocrine Tumor Program; assistant professor of medicine, UChicago Medicine, discusses key considerations for the selection of single-agent vs combination regimens for patients with metastatic hepatocellular carcinoma (HCC) in the front line.

The first-line treatment armamentarium in HCC has expanded significantly, with several doublet regimens now FDA approved, Liao begins. These include combinations such as atezolizumab (Tecentriq) and bevacizumab (Avastin), as well as durvalumab (Imfinzi) and tremelimumab (Imjudo), he details.

Additionally, positive results from the phase 3 CheckMate-9DW study (NCT04039607) evaluating the combination of ipilimumab (Yervoy) and nivolumab (Opdivo) were presented at the 

, Liao reports. These data will likely support the combination's FDA approval in the near future, he adds.

With multiple regimens to choose from, the general approach for fit patients, those with good liver function (Child-Pugh A), and without contraindications, is to administer doublet therapy rather than monotherapy, Liao states. Doublet therapy is generally more effective than monotherapy, as according to the current body of evidence. However, in certain situations where patients may have contraindications to a certain drug, are frailer, or have poor liver function, monotherapy might be the preferred option, Liao explains.

Deciding between immuno-oncology (IO) plus TKI combinations vs IO/IO regimens requires consideration of the patient's overall health and comorbidities, Liao continues. For instance, patients with significant cardiovascular comorbidities, such as uncontrolled hypertension, may not be suitable candidates for anti-VEGF therapy, he says. In such cases, an IO-IO regimen might be more appropriate, Liao advises.

Given the lack of head-to-head comparisons between these approaches, treatment decisions are currently individualized based on what is deemed the best fit for the patient, Liao emphasizes. This individualized approach accounts for the patient's specific health conditions and potential treatment-related toxicities, he concludes.

Chih-Yi Liao, MD, assistant professor of medicine, University of Chicago Department of Medicine, discusses outcomes reported with ivosidenib (Tibsovo) in patients with advanced cholangiocarcinoma.

In the phase 3 ClarIDHy trial (NCT02989857), the agent was examined vs placebo in patients with 

-mutant, advanced cholangiocarcinoma. The primary end point of the trial was progression-free survival (PFS), which was met, according to Liao. Ivosidenib resulted in a PFS of 2.7 months vs 1.4 months with placebo in this population, Liao says. Although this may not seem numerically significant, it translates a 63% reduction in the risk of progression or death, Liao notes.

In terms of overall survival (OS), the median OS in patients who received treatment with ivosidenib was 10.3 months vs 7.5 months in those who were given placebo, Liao adds. Despite the numeric improvement, this was not found to be statistically significant, Liao concludes.

Chih-Yi Liao, MD, discusses outcomes reported with ivosidenib in patients with advanced cholangiocarcinoma.


Chih-Yi Liao, MD

Articles

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

Dr Liao on Selecting Between First-Line Monotherapy and Combination Approaches in HCC

Dr. Liao on Outcomes With Ivosidenib in Advanced Cholangiocarcinoma