Targeted Drug Therapy for Bile Duct Cancer
Targeted therapies are medicines that are directed at, or target, cancer cells that have certain gene or protein changes that help the cancer cells grow, spread, and live longer. Targeted drugs work to destroy cancer cells or slow their growth. The side effects from these drugs are different from chemotherapy, and sometimes less severe.
Several types of targeted therapy drugs can be used to treat bile duct cancer. Biomarker testing before treatment can help show whether these drugs are likely to be helpful.
Targeted drugs work differently from standard chemotherapy (chemo) drugs. And they often have different side effects.
FGFR2 inhibitors
FGFR2 is a protein on cells that helps them grow and divide. Some people with bile duct cancer that starts inside the liver have a change called an FGFR2 fusion, where the FGFR2 gene is joined to part of another gene. This makes an abnormal FGFR2 protein that helps the cancer cells grow.
FGFR inhibitors can be used to treat advanced bile duct cancers that can't be removed with surgery or that have spread to distant parts of the body. They're usually used after other treatments, such as chemotherapy, have stopped working.
These drugs only work if your cancer has an FGFR2 fusion. Your doctor will test your cancer for this change before you start one of these drugs.
Pemigatinib (Pemazyre) and futibatinib (Lytgobi) are FGFR2 inhibitors. They block the abnormal FGFR2 protein in bile duct cancer cells and keep them from growing and spreading to other places.
These drugs are taken by mouth as tablets, typically once a day.
The most common side effects of FGFR inhibitors include:
- Digestive problems, including diarrhea, constipation, nausea, vomiting, abdominal (belly) pain, dry mouth or mouth sores, loss of appetite, taste changes
- Skin, hair and nail issues, including hair loss, nail changes, dry skin, hand-foot syndrome
- Dry eye or other eye problems, including a problem with the retina that can cause blurred vision
- High levels of phosphate in the blood
- Joint, muscle, or back pain
- Fatigue
IDH1 inhibitor
In some bile duct cancers, the cancer cells have a change (mutation) in the IDH1 gene. This gene normally helps cells make the IDH1 protein. Changes in this gene can lead to an abnormal IDH1 protein, which can stop cells from growing into healthy, mature cells.
This gene change happens in about 15% of intrahepatic bile duct cancers. It is rare in perihilar and distal bile duct cancer.
These inhibitors can be used in people with advanced, previously treated bile duct cancer.
These drugs only work if your cancer cells have an IDH1 mutation. Your doctor can test your cancer cells to see if they have an IDH1 mutation.
Ivosidenib (Tibsovo) is an IDH1 inhibitor. It blocks the abnormal IDH1 protein. This seems to help the cancer cells shift and grow into more normal, healthy cells.
It is taken by mouth, once a day.
Common side effects can include:
- Fatigue
- Nausea and/or vomiting
- Abdominal (belly) pain or swelling
- Diarrhea
- Loss of appetite
- Cough
- Low red blood cell counts (anemia)
- Rash
- Changes in lab tests showing the drug is affecting the liver
Less common but more serious side effects can include:
- Changes in heart rhythm
- Pneumonia
- Jaundice (yellowing of the eyes and skin)
TRK inhibitors
A very small number of bile duct cancers have changes called an NTRK gene fusion. A gene fusion happens when part of one gene joins with part of another gene. In this case, the fusion makes an abnormal TRK protein that is always turned on, which helps the cancer cells grow.
NTRK inhibitors can be used to treat advanced bile duct cancer that has an NTRK gene fusion. They can be used in people who has not received prior systemic therapy. These drugs only work if your cancer has an NTRK fusion, so your cancer will need to be tested for this change.
Larotrectinib (Vitrakvi), entrectinib (Rozlytrek), and repotrectinib (Augtyro) are TRK inhibitors. TRK inhibitors target and disable the proteins made by the NTRK genes.
These drugs are taken as pills, once or twice daily.
Common side effects can include:
- Liver test results that are outside the normal range
- Decreased white blood cell and red blood cells
- Muscle and joint pain
- Tiredness
- Diarrhea or constipation
- Nausea and vomiting
- Stomach pain
Less common but more serious side effects can include:
- Mental changes such as confusion, changes in mood, and changes in sleep
- Liver damage
- Changes in heart rhythm and/or function
- Vision changes
- Harm to an unborn baby
RET inhibitors
In a small number of bile duct cancers, the tumor cells have a rearrangement in the RET gene. It causes them to make an abnormal form of the RET protein. This abnormal protein helps tumor cells grow.
RET inhibitors can be used to treat advanced bile duct cancers with the RET rearrangement.
Selpercatinib (Retevmo) and pralsetinib (Gavreto) are RET inhibitors.
These drugs are taken by mouth as capsules, typically once or twice a day.
Common side effects can include:
- Dry mouth
- Diarrhea or constipation
- High blood pressure
- Tiredness
- Swelling in hands and/or feet
- Skin rash
- Muscle and joint pain
- Low blood cell counts or changes in other blood tests
Less common but more serious side effects can include:
- Liver damage
- Lung damage
- Allergic reactions
- Changes in heart rhythm
- Bleeding easily
- Problems with wound healing
BRAF inhibitor and MEK inhibitor
Some bile duct cancers have changes in the BRAF gene. Cells with these gene changes make an altered BRAF protein that helps them grow. Some drugs target this and other related proteins. A combination of a BRAF inhibitor and a MEK inhibitor is often given together to treat advanced cancer with the BRAF V600E gene change.
This drug combination can be used in people with advanced, previously treated bile duct cancer with the BRAF V600E gene change.
Dabrafenib (Tafinlar) is a BRAF inhibitor. Trametinib (Mekinist) is a MEK inhibitor.
These drugs are taken as pills or capsules each day.
Common side effects can include:
- Skin and hair issues, including hair loss, skin thickening, rash, itching, and sensitivity to the sun
- Flu-like symptoms, including headache, fever, joint pain and tiredness
- Digestive issues, such as nausea and diarrhea
Less common but more serious side effects can include:
- Bleeding
- Heart rhythm problems
- Liver or kidney problems
- Lung problems
- Severe allergic reactions
- Severe skin or eye problems
- Increased blood sugar levels
- Squamous cell skin cancer
KRAS inhibitor
In some bile duct cancers, the cancer cells have changes in the KRAS gene. This is called a KRAS G12C mutation. The change causes the cell to create an abnormal form of the KRAS protein, which helps the cancer cells grow and spread.
KRAS inhibitors attach to the KRAS G12C protein. They help keep cancer cells from growing.
It is given to people with advanced bile duct cancer who have already had at least one other type of drug treatment.
Adagrasib (Krazati) is a KRAS inhibitor used to treat advanced bile duct cancer with the KRAS G12C mutation.
This drug is taken as a pill, typically twice a day.
Common side effects can include:
- Diarrhea
- Nausea and vomiting
- Muscle pain
- Fatigue
- Cough
- Decreased white blood cell and red blood cell counts
- Changes in other blood tests
Less common but more serious side effects can include:
- Kidney or liver damage
- Lung damage called interstitial lung disease (ILD)/pneumonitis
- A heart condition called QTc interval prolongation
HER2 inhibitor
Some bile duct cancers have too much of the HER2 protein on the surface of their cells, which can help cancer cells grow. Having too much of this protein is caused by having too many copies of the HER2 gene. Cancers with increased levels of HER2 are called HER2-positive.
HER2 inhibitors can be used to treat HER2-positive bile duct cancer that can’t be removed completely or that has spread to other parts of the body. This medicine is used after other treatments have already been tried.
Zanidatamab (Ziihera) is a medicine that attaches to 2 different parts of the HER2 protein.
This drug is given as an infusion into a vein (IV), typically once every 2 weeks.
Some people might have an infusion reaction while receiving this drug. This is like an allergic reaction, and can include fever, chills, flushing of the face, rash, itchy skin, feeling dizzy, wheezing, and trouble breathing. It’s important to tell your doctor or nurse right away if you have any of these symptoms while getting this drug. You will be given medicines before each infusion to help lower this risk.
This drug can cause heart damage in some people. Before and during treatment with this drug, your doctor will test your heart function with an echocardiogram or a MUGA scan. These tests show how well your heart is pumping blood.
This drug can cause diarrhea, which might be severe. It’s very important to let your healthcare team know about any changes in your bowel habits as soon as they happen.
Other side effects of this drug can include stomach pain and feeling very tired.
HER2-targeted antibody-drug conjugate
Some bile duct cancers have too much HER2 protein on the surface of their cells, which can help cancer cells grow. Having too much of this protein is caused by having too many copies of the HER2 gene. Cancers with increased levels of HER2 are called HER2-positive.
This can be used to treat HER2-positive bile duct cancer that can't be removed completely or has spread. It is used in people who have already tried other treatments.
Trastuzumab deruxtecan (Enhertu) is a different type of HER2-targeted drug called an antibody-drug conjugate. It's made of a HER2-targeting antibody attached to a chemotherapy drug. The antibody part finds and attaches to the HER2 protein on cancer cells. Then it delivers the chemotherapy directly into those cells.
This drug is given as an infusion into a vein (IV), typically once every 3 weeks.
Common side effects can include low blood cell counts, nausea, fatigue, hair loss, diarrhea, constipation, loss of appetite, and changes in liver function tests.
Serious but less common side effects include lung damage (either interstitial lung disease or pneumonitis), which can be severe or life-threatening. Tell your healthcare team right away if you develop new or worsening cough, shortness of breath, or fever. This drug can also cause harm to an unborn baby.
HER2 and HER3 inhibitor
In some bile duct cancers, the cancer cells have a change in the NRG1 gene called a fusion mutation. This mutation makes an abnormal form of the NRG1 protein, which binds to the HER3 protein and signals the cancer cells to grow.
These drugs can be used to treat bile duct cancer with a NRG1 fusion mutation that can’t be removed completely or that has spread to other parts of the body. They are used after at least one other drug treatment has already been tried.
Zenocutuzumab (Bizengri) is a bispecific antibody that binds to the HER2 and HER3 proteins on the surface of cancer cells and prevents the NRG1 protein from binding to HER3.
This drug is given as an infusion into a vein (IV), typically once every 2 weeks.
Some people might have an infusion reaction while getting this drug. This is like an allergic reaction, and can include fever, chills, flushing of the face, rash, itchy skin, feeling dizzy, wheezing, and trouble breathing. It’s important to tell your doctor or nurse right away if you have any of these symptoms while getting this drug. You will be given medicines before each infusion to help lower this risk.
Common side effects of this drug can include:
- Nausea and/or vomiting
- Abdominal pain, diarrhea, and/or constipation
- Muscle and joint pain
- Fatigue
- Rash
- Swelling
Less common but more serious side effects can include changes in blood tests, such as:
- Low red cell count
- Low platelet count
- Low sodium level
- High liver function test values
More information about targeted therapy
To learn more about how targeted drugs are used to treat cancer, see Targeted Cancer Therapy.
To learn about some of the side effects listed here and how to manage them, see Managing Cancer-related Side Effects.
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- References
Developed by the American Cancer Society medical and editorial content team with medical review and contribution by the American Society of Clinical Oncology (ASCO).
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Meric-Bernstam F, Makker V, Oaknin A, et al. Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing solid tumors: primary results from the DESTINY-PanTumor02 phase II trial. J Clin Oncol. 2024;42(1):47-58.
Moris D, Palta M, Kim C, Allen PJ, Morse MA, Lidsky ME. Advances in the treatment of intrahepatic cholangiocarcinoma: An overview of the current and future therapeutic landscape for clinicians. CA Cancer J Clin. 2023;73(2):198-222.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Biliary Tract Cancers. Version 1.2026. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/btc.pdf on September 9, 2026.
Last Revised: October 27, 2026
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