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As researchers learn more about the changes in cells that cause cancer, they've developed drugs to target some of these changes. These targeted drugs work differently from standard chemotherapy (chemo) drugs, and they often have different side effects. This type of treatment blocks the growth and spread of cancer cells and limits damage to healthy cells.

FGFR2 inhibitors

FGFRs (fibroblast growth factor receptors) are proteins on cells that help them grow and divide normally. A small number of people with bile duct cancer within the liver have changes in the genes that make FGFRs. These changes result in abnormal FGFR proteins that cause cells to grow out of control and turn into cancer.

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 can be used to treat some advanced bile duct cancers that cannot be removed by surgery or have spread to distant areas after at least one previous chemotherapy treatment. For these drugs to work, your cancer must have an abnormal FGFR2 gene, so your cancer will be tested before you start any of these drugs.

These medicines are taken by mouth as tablets, typically once a day.

Possible side effects of FGFR2 inhibitors

The most common side effects of FGFR2 inhibitors include kidney problems, hair loss, diarrhea, constipation, nail problems, fatigue, taste changes, nausea, vomiting, dry mouth or mouth sores, loss of appetite, dry skin, dry eye or other eye problems, hand-foot syndrome, abdominal (belly) pain, and changes in blood mineral levels.

IDH1 inhibitor

In some people with bile duct cancer (about 15% of patients), the cancer cells have a change (mutation) in the IDH1 gene, which normally helps cells make the IDH1 protein. Mutations in this gene can lead to an abnormal IDH1 protein, which can stop cells from maturing the way they normally would.

Ivosidenib (Tibsovo) is an IDH1 inhibitor. It blocks the abnormal IDH1 protein, which seems to help the cancer cells mature into more normal cells. This drug can be used in people with advanced, previously treated bile duct cancer if the cancer cells are found to have an IDH1 mutation. Your doctor can test your cancer cells to see if they have an IDH1 mutation.

This drug is taken by mouth, once a day.

Possible side effects of IDH1 inhibitor

Common side effects can include fatigue, nausea, vomiting, abdominal (belly) pain or swelling, diarrhea, loss of appetite, cough, low red blood cell counts (anemia), rash, and 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, and jaundice (yellowing of the eyes and skin).

NTRK inhibitor

A very small number of bile duct cancers have changes in one of the NTRK genes, called NTRK gene fusions. A gene fusion is when 2 separate genes join together and don't function normally as a result. Cells with these gene changes make abnormal TRK proteins, which can lead to abnormal cell growth and cancer.

Larotrectinib (Vitrakyi) or entrectinib (Rozlytrek) are NTRK inhibitors. TRK inhibitors target and disable the proteins made by the NTRK genes. This drug can be used in people with advanced bile duct cancer who have not received prior systemic therapy.

These drugs are taken as pills, once or twice daily.

Possible side effects of NTRK inhibitors

Common side effects can include abnormal liver tests; decreased white blood cell and red blood cells; muscle and joint pain; tiredness; diarrhea or constipation; nausea and vomiting; and 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; and harm to a fetus.

RET inhibitor

In a small percentage of bile duct cancers, the tumor cells have a rearrangement in the RET gene that cause them to make an abnormal form of the RET protein. This abnormal protein helps the tumor cells grow. 

Selpercatinib (Retevmo) or pralsetinib (Gayreto) are RET inhibitors and can be used to treat advanced bile duct cancers with the RET rearrangement.

These drugs are taken by mouth as capsules, typically once or twice a day.

Possible side effects of RET inhibitors

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, and problems with wound healing.

BRAF inhibitor

In some bile duct cancers, the cells have changes in the BRAF gene. Cells with these 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 mutation.

Dabrafenib (Tafinlar) is a BRAF inhibitor. Trametinib (Mekinist) is a MEK inhibitor. This drug combination can be used in people with advanced, previously treated bile duct cancer if the cancer cells are found to have a BRAF V600E mutation.

These drugs are taken as pills or capsules each day.

Possible side effects of BRAF inhibitor

Common side effects can include skin thickening, rash, itching, sensitivity to the sun, headache, fever, joint pain, tiredness, hair loss, 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, and squamous cell skin cancer.

KRAS inhibitor

In some bile duct cancers, the cancer cells have changes in the KRAS gene called a KRAS G12C mutation. This mutation makes an abnormal form of the KRAS protein, which helps the cancer cells grow and spread. KRAS inhibitors attach to the KRAS G12C protein, which helps keep cancer cells from growing.

Adagrasib (Krazati) is a KRAS inhibitor and is used to treat advanced bile duct cancer with the KRAS G12C mutation in people who’ve already had at least one other type of drug treatment.

This drug is taken as a pill, typically twice a day.

Possible side effects of KRAS inhibitor

Common side effects can include diarrhea, nausea and vomiting, muscle pain, fatigue, cough, decreased white blood cell and red blood cell counts, and changes in other blood tests.

Less common but more serious side effects can include kidney damage, liver damage, lung damage called interstitial lung disease (ILD)/pneumonitis, and a heart condition called QTc interval prolongation.