BiomarkersCholangiocarcinomaGenetics & CancerGenomic Testing

Biomarker Testing Crucial for Patients with Cholangiocarcinoma

New treatments are becoming available for patients with cholangiocarcinoma (bile duct cancer). Testing for specific biomarkers is crucial to ensure each patient receives the best available treatment for any associated biomarker.
May 2020 – Biomarkers & Genetic Testing
Wayne Kuznar

Cholangiocarcinoma is a rare cancer that starts in the bile duct (which is part of the gastrointestinal system). It is, therefore, often referred to by researchers and by oncologists as bile duct cancer. Bile ducts are thin tubes that connect your liver, gallbladder, and small intestine.

According to the National Cancer Institute, cholangiocarcinoma is a rare cancer, currently representing only 2.4% of all new cancers diagnosed in the United States. Because its signs and symptoms often go unnoticed, bile duct cancer (or cholangiocarcinoma) is usually detected at a later stage, when the cancer has advanced and surgical removal of the tumor (which may offer a cure) is less likely to be successful.

The current standard of therapy for patients with advanced cholangiocarcinoma is chemotherapy with gemcitabine plus cisplatin. However, the prognosis (or outlook) for patients with advanced-stage cholangiocarcinoma with chemotherapy is poor.

Why Is Testing So Important?

Recently, advances in personalized medicine and genomic or biomarker testing are gradually making new treatments available for patients with cholangiocarcinoma. The use of testing for specific biologic markers (or biomarkers) is improving outcomes for patients with this type of cancer.

Testing for genomic mutations and other biomarkers for cholangiocarcinoma, such as MSI-H or MMRd, are allowing patients with this disease to have access to newer treatments, such as immunotherapy with Keytruda (pembrolizumab), which is not available without biomarker testing for patients with this cancer. Keytruda is approved for many types of cancer, as well as for all solid cancers (such as cholangiocarcinoma) that have the MSI-H or MMRd biomarker.

Most of these newer targeted therapies are not yet approved for the treatment of patients with cholangiocarcinoma and are only available through participation in clinical trials.

Therefore, it is crucial that patients with cholangiocarcinoma undergo biomarker testing early on, to see if they are qualified to participate in a clinical trial that is investigating one of these newer targeted treatments that are associated with specific genomic abnormalities.

Stacie Lindsey

In an interview with Stacie Lindsey, CEO and Founder of the Cholangiocarcinoma Foundation, she explained that cholangiocarcinoma has one of the highest number of gene mutations (abnormal changes) among all gastrointestinal cancers.

According to Ms. Lindsey, many of these mutations can be treated with targeted therapies (that target the specific mutation) and are available through a clinical trial only. Many other mutations are currently being investigated by researchers.

Ms. Lindsey’s brother was diagnosed with cholangiocarcinoma in late 2005 and passed away in January 2007. She had advocated for her brother, done extensive research on available treatment options, and was networking with other patients, cancer researchers, and healthcare professionals.

Before her brother passed away, he wanted to make sure that patients with cholangiocarcinoma who don’t have such family help would have access to all the research that had already been done on this rare cancer. So, the family set up the Cholangiocarcinoma Foundation to provide help.

All Patients Should Have Biomarker Testing

“Every patient with cholangiocarcinoma should have biomarker testing, which will allow them to know all the possible treatment options available to them,” said Ms. Lindsey.

Testing for biomarkers scans the DNA of cancer cells for cancer-causing genomic mutations and other molecular abnormalities. The information from this testing can be used to match a patient’s cancer biomarkers with the most effective treatment available today, including targeted therapies or immunotherapy.

The Cholangiocarcinoma Foundation has a video campaign called Mutations Matter that encourages biomarker testing for all patients with cholangiocarcinoma (available online at

The foundation has been participating in an international working group called the Consistent Tumor Testing Terminology, which consists of advocacy, professional associations, medical professionals, regulatory bodies and corporate and industry partners. The group is advocating the use of the umbrella term “biomarker testing” as a patient-focused term to describe molecular profiling and other tests for acquired mutations, which are caused by abnormal cell development and are known as “somatic” mutations.

Biomarker testing can be underappreciated in the community oncology setting, noted Ms. Lindsey. “Some professionals don’t understand that biomarker testing is informative testing, not reactive testing,” she said. By informative testing, she means that the results of the test can inform or guide the pathway to select the best treatment for the individual patient.

“We don’t currently have a good standard of care for this cancer, which means a clinical trial is part of the treatment pathway. Getting biomarker testing is the only way to access many of these clinical trials,” Ms. Lindsey pointed out.

Guiding Therapy with Biomarker Testing

About 50% of patients with cholangiocarcinoma have a mutation that can be targeted with existing or experimental targeted therapies or immunotherapy. Several therapies are now in advanced, phase 3, clinical trials, and the first treatment for cholangiocarcinoma was just very recently approved for this rare cancer.

In April 2020, Pemazyre (pemigatinib) became the first ever drug approved for the treatment of patients with advanced or metastatic cholangiocarcinoma whose tumor has the FGFR2 biomarker.

In addition, 2 investigational drugs—infigratinib and futibatinib —have shown success in clinical trials in patients with advanced cholangiocarcinoma and an FGFR gene translocation or other alterations that were found through biomarker testing.

Infigratinib is currently under a fast-track review by the FDA as potential first-line treatment for patients with advanced or metastatic cholangiocarcinoma associated with an FGFR gene alteration.

These 3 drugs are known as FGFR inhibitors, meaning that they target the FGFR biomarker to block and inhibit its activity, which encourages the progression of cancer cells.

Furthermore, patients with advanced cholangiocarcinoma who are found to have the IDH1 genetic mutation through biomarker testing may soon have a promising new treatment option (according to results from a phase 3 clinical trial) with the targeted therapy Tibsovo (ivosidenib), which blocks the activity of the IDH1 mutation and is approved for other types of cancer.

Although biomarker testing is not yet routine for patients with cancer, it is gradually becoming more common in oncology. Furthermore, the cost of testing is now covered for all older patients with Medicare insurance who have advanced solid tumors, which further encourages the use of such testing.

Biomarker testing is routinely offered at academic medical centers, which often run clinical trials, and biomarker testing is often used as part of clinical trial protocols. For patients who are not living near a major medical center, this can be an obstacle to having biomarker testing.

Biomarker Testing Should Be Done Early

For patients with advanced cholangiocarcinoma that cannot be removed by surgery, the standard of care is chemotherapy. However, the disease often progresses within a few months. Patients should have biomarker testing immediately after diagnosis, so when the disease progresses, they are ready with the next available treatment option.

Waiting until the cancer progresses before undergoing a biomarker test can be a waste of valuable time, because testing results can often take weeks, according to Ms. Lindsey.

“There’s no reason patients shouldn’t have the testing done immediately after diagnosis,” she said. “If a patient decides to go with the standard of care, that’s fine, but they should have the testing done, so they are ready to take next steps when needed.”

Several newer types of genomic or biomarker testing are available today, including next-generation sequencing and liquid biopsy. Patients should ask their doctors which type of biomarker or genomic testing is best for them, and why.

Consider Joining a Clinical Trial

Melinda Bachini

Melinda Bachini is the Advocacy Coordinator at the Cholangiocarcinoma Foundation and a 10-year survivor of cholangiocarcinoma. In an interview, Ms. Bachini said that in her case, biomarker testing was done as part of a clinical trial sponsored by the National Cancer Institute. This allowed her to receive therapy that is normally not available to patients with cholangiocarcinoma.

“It was adoptive-cell therapy. Ultimately, they ended up profiling my tumor, and testing my T-cells against it to find a reactive T-cell against one of my mutations,” Ms. Bachini said.

“Further down the road, when the cancer started growing again, they went back and profiled the tumor again, and found the presence of the PD-L1 protein. I ended up taking Keytruda. So, it definitely made a difference for me. It is the reason I am here 10 years later,” she said.

Keytruda is an immunotherapy that works for cancers that express the PD-L1 protein, including in patients with cholangiocarcinoma. Keytruda is not yet approved by the FDA for the treatment of patients with cholangiocarcinoma specifically and is available for these patients through clinical trials.

“Biomarker testing can provide more options for treatment, including clinical trials. I am alive today because of a clinical trial,” Ms. Bachini emphasized.

According to Ms. Bachini, between 1% and 3% of patients with cholangiocarcinoma have a biomarker, such as MSI-H or MMRd, that is associated with the tumor and can be found with biomarker testing. This knowledge can make them able to receive treatment with a therapy that can block these types of biomarkers and improve their outcomes.

Key Points

  • Many patients with cholangiocarcinoma have a genetic mutation or other biomarkers that may benefit from targeted therapies or immunotherapies
  • Biomarker testing should be done at diagnosis instead of waiting until the cancer has progressed
  • FGFR inhibitors target the FGFR gene translocations to block its activity that encourages cancer cells progression
  • In April 2020, Pemazyre became the first drug to be approved for the treatment of patients with advanced cholangiocarcinoma and the FGFR2 biomarker
  • The other 2 FGFR inhibitors, infigratinib and futibatinib, have also shown success in clinical trials in the treatment of cholangiocarcinoma associated with the FGFR biomarker
  • Several types of biomarker tests are available, so ask your doctor which test is best for you

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Last modified: March 10, 2022

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