Targeted Drug Therapy for Bile Duct Cancer

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. 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 (about 15%) of people with bile duct cancer within the liver 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 infigratinib (Truseltiq) 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 starting either of these drugs.

Pemigatinib is given as a tablet by mouth once a day for 2 weeks, followed by one week off, then started again. Infigratinib is given as a tablet once a day for 3 weeks, followed by one week off, then started again. 

Possible side effects of FGFR2 inhibitors

The most common side effects of FGFR2 inhibitors are having too much or too little phosphate in the blood, 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, and abdominal (belly) pain.

IDH1 inhibitor

In some people with bile duct 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 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 ivosidenib

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).

More information about targeted therapy

To learn more about how targeted drugs are used to treat cancer, see Targeted Therapy.

To learn about some of the side effects listed here and how to manage them, see Managing Cancer-related Side Effects.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Abou-Alfa GK, Sahai V, Hollebecque A, Vaccaro G, Melisi D, Al-Rajabi R, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 2020 May;21(5):671-684. doi: 10.1016/S1470-2045(20)30109-1. Epub 2020 Mar 20.

DeLeon TT, Ahn DH, Bogenberger JM, et al. Novel targeted therapy strategies for biliary tract cancers and hepatocellular carcinoma. Future Oncol. 2018;14(6):553-566.

Hoyos S, Navas M-C, Restrepo J-C, Botero RC. Current controversies in cholangiosarcoma. BBA - Molecular Basis of Dis. 2108;1864:1461-1467.

Lombardi P, Marino D, Fenocchio E, et al. Emerging molecular target antagonists for the treatment of biliary tract cancer. Expert Opinion on Emerging Drugs. 2018;23(1):63-75.

National Comprehensive Cancer Network, Clinical Practice Guidelines in Oncology (NCCN Guidelines®), Hepatobiliary Cancers, Version 2.2018 -- June 7, 2018. Accessed at www.nccn.org/professionals/physician_gls/pdf/hepatobiliary.pdf on June 26, 2018.

Rizvi S, Khan SA, Hallemeier CL, Kelley RK, Gores GJ. Cholangiocarcinoma: Evolving concepts and therapeutic strategies. Nat Rev Clin Oncol. 2018;15(2):95-111.

Valle JW, Lamarca A, Goyal L, Barriuso J, Zhu AX. New Horizons for Precision Medicine in Biliary Tract Cancers. Cancer Discov. 2017;7(9):943-962.  

References

Abou-Alfa GK, Sahai V, Hollebecque A, Vaccaro G, Melisi D, Al-Rajabi R, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 2020 May;21(5):671-684. doi: 10.1016/S1470-2045(20)30109-1. Epub 2020 Mar 20.

DeLeon TT, Ahn DH, Bogenberger JM, et al. Novel targeted therapy strategies for biliary tract cancers and hepatocellular carcinoma. Future Oncol. 2018;14(6):553-566.

Hoyos S, Navas M-C, Restrepo J-C, Botero RC. Current controversies in cholangiosarcoma. BBA - Molecular Basis of Dis. 2108;1864:1461-1467.

Lombardi P, Marino D, Fenocchio E, et al. Emerging molecular target antagonists for the treatment of biliary tract cancer. Expert Opinion on Emerging Drugs. 2018;23(1):63-75.

National Comprehensive Cancer Network, Clinical Practice Guidelines in Oncology (NCCN Guidelines®), Hepatobiliary Cancers, Version 2.2018 -- June 7, 2018. Accessed at www.nccn.org/professionals/physician_gls/pdf/hepatobiliary.pdf on June 26, 2018.

Rizvi S, Khan SA, Hallemeier CL, Kelley RK, Gores GJ. Cholangiocarcinoma: Evolving concepts and therapeutic strategies. Nat Rev Clin Oncol. 2018;15(2):95-111.

Valle JW, Lamarca A, Goyal L, Barriuso J, Zhu AX. New Horizons for Precision Medicine in Biliary Tract Cancers. Cancer Discov. 2017;7(9):943-962.  

Last Revised: August 26, 2021

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