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As researchers learn more about the changes in cells that cause gallbladder cancer, they've developed drugs to target some of these changes. These targeted drugs work differently from standard chemotherapy (chemo) drugs. They sometimes work when standard chemo drugs don’t, and they often have different side effects.

FGFR2 inhibitors

FGFRs (fibroblast growth factor receptors) are proteins on cells that help them grow and divide normally. A small number of people with gallbladder cancer have changes in the genes that make FGFRs, which 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 gallbladder cancer cells and keep them from growing and spreading to other places.

These drugs can be used to treat some advanced gallbladder 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 starting 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 gallbladder cancer, 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 gallbladder 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).

TRK inhibitors

A very small number of gallbladder cancers have changes in one of the NTRK genes, called NTRK gene fusions. Cells with these gene changes make abnormal TRK proteins, which can lead to abnormal cell growth and cancer.

Larotrectinib (Vitrakyi), entrectinib (Rozlytrek), and repotrectinib (Augtyro) are TRK inhibitors. TRK inhibitors target and disable the proteins made by the NTRK genes. These drugs can be used in people with advanced gallbladder cancer, who have not received prior systemic therapy.

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

Possible side effects of TRK 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, changes in sleep; liver damage; changes in heart rhythm and/or function; vision changes; harm to a fetus.

RET inhibitors

In a small percentage of gallbladder cancers, the tumor cells have 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) and pralsetinib (Gayreto) are RET inhibitors and can be used to treat advanced gallbladder 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 and MEK inhibitor

In some gallbladder 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 related proteins. A combination of 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 gallbladder cancer, if the cancer cells are found to have an BRAF V600E mutation.

These drugs are taken as pills or capsules each day.

Possible side effects

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 gallbladder 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 gallbladder cancer with the KRAS G12C mutation if you’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) or pneumonitis, and a heart condition called QTc interval prolongation.

HER2 inhibitor

Some gallbladder 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.

Zanidatamab (Ziihera) is a medicine that attaches to 2 different parts of the HER2 protein. It can be used to treat HER2-positive gallbladder cancer that can’t be removed completely or that has spread to other parts of the body, if other treatments have already been tried.

This drug is given as an infusion into a vein (IV), typically once every 2 weeks.

Possible side effects

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.

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.

This drug can cause diarrhea, which might be severe, so it’s very important to let your health care 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.