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Targeted drug therapy is directed (targeted) at proteins on vaginal cancer cells that help them grow, spread, or live longer. Targeted drugs work to destroy cancer cells or slow down their growth.  Some targeted therapy drugs, for example, monoclonal antibodies, work in more than one way to control cancer cells and can also be considered immunotherapy because they boost the immune system.  Different types of targeted drug therapy can be used to treat vaginal cancer.

Antibody-drug conjugates

An antibody-drug conjugate (ADC) is a monoclonal antibody linked to a chemotherapy drug. The antibody acts like a homing signal by attaching to a target protein on cancer cells, so that the chemo can be brought directly to the cancer cell.

Fam-trastuzumab deruxtecan, T-DXd (Enhertu): This ADC connects the anti-HER2 antibody to the chemo drug, deruxtecan. T-DXd can be used by itself to treat late-stage vaginal cancer that is HER2 positive and has recurred after initial systemic treatment.

This drug is given in a vein (IV) typically once every 3 weeks.

Common side effects include low blood cell counts, nausea/vomiting, diarrhea, fatigue, hair loss, decreased appetite, low potassium level, changes in liver function tests, and cough.

A less common but serious side effect is decreased heart muscle strength, which is a condition called left ventricular dysfunction.

Tisotumab vedotin-tftv (Tivdak): This ADC has an antibody that targets tissue-factor (TF) protein on cancer cells. It brings the chemo drug, monomethyl auristatin E (MMAE), directly to the cancer cell. This drug was studied in people with cervical cancer. Since vaginal cancer is relatively uncommon and lacks data, chemo drugs approved for cervical cancer are commonly used to treat vaginal cancer as well. Tisotumab vedotin can be used by itself to treat late-stage vaginal cancer that has come back, after initial chemo treatment.

This drug is given in a vein (IV) typically once every 3 weeks.

Common side effects can include feeling tired, nausea, vomiting, hair loss, bleeding, diarrhea, rash, nerve damage (peripheral neuropathy), abnormal kidney function, or low blood cell counts.

Less common but serious side effects can include vision change or loss. People should have regular eye exams while taking this drug and tell their healthcare team right away if they have any eye symptoms.

RET inhibitors

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

Selpercatinib (Retevmo) targets the enzyme that makes cancer cells grow and can be used to treat advanced vaginal cancer with the RET rearrangement.

These drugs are capsules taken by mouth, typically 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, and problems with wound healing.

NTRK inhibitors

A very small number of vaginal 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) and 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 vaginal cancer.

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

Common side effects can include abnormal liver test results; decreased white blood cells 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.