Targeted Drug Therapy for Thyroid Cancer

In recent years, doctors have begun using newer, targeted drugs to treat thyroid cancer.

Targeted drugs are different from standard chemotherapy (chemo) drugs, and they are usually more likely to work. They often have different side effects, as well.

What is targeted drug therapy?

Standard chemo drugs work by attacking rapidly growing cells, including cancer cells. But targeted drugs attack specific gene and protein changes inside thyroid cancer cells. These gene and protein changes are what make the cancer cells different from normal cells.

The types of targeted drugs used to treat thyroid cancer are known as kinase inhibitors. Kinases are proteins inside cells that normally relay signals (such as telling the cell to grow). Blocking certain kinases can help treat some cancers.

Targeted drugs for papillary or follicular thyroid cancer

Most of these cancers can be treated with surgery and radioactive iodine therapy. But when those treatments aren’t effective, targeted drugs can often be helpful.

Multikinase inhibitors

Lenvatinib (Lenvima), sorafenib (Nexavar), and cabozantinib (Cabometyx) are targeted drugs known as multikinase inhibitors, because they block several different kinase proteins. These drugs work in 2 main ways:

• They help block tumors from forming new blood vessels, which the tumors need to grow.
• They target some of the proteins made by cancer cells that normally help them grow.

Lenvatinib and sorafenib can often help stop cancer growth for a time in people with papillary or follicular thyroid cancer whose radioactive iodine treatment is no longer working. If these drugs are no longer helpful, cabozantinib may be an option.

All of these drugs are taken by mouth.

Common side effects can include fatigue, rash, loss of appetite, diarrhea, nausea, high blood pressure, and hand foot syndrome (redness, pain, swelling, or blisters on the palms of the hands or soles of the feet). Other more serious side effects, such as severe bleeding and holes in the intestine, can also occur.

Ask your health care team what to expect.

RET inhibitors

In some papillary and follicular thyroid cancers, the cells have certain changes in the RET gene that cause them to make an abnormal from of the RET kinase protein. This abnormal protein helps the cells grow.

Selpercatinib (Retevmo) and pralsetinib (Gavreto) are drugs known as RET inhibitors. They work by attacking the RET protein. These drugs can be used to treat advanced papillary or follicular thyroid cancer if the cancer cells have certain types of RET gene changes, and radioactive iodine therapy is not a good option.

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

Common side effects can include dry mouth, diarrhea, constipation, high blood pressure, feeling tired, swelling in the hands or feet, skin rash, high blood sugar levels, low white blood cell or blood platelet counts, and changes in certain other blood tests.

Less common but more serious side effects can include liver damage, allergic reactions, changes in heart rhythm, bleeding easily, and problems with wound healing.

TRK inhibitors

A small number of thyroid cancers have changes in one of the NTRK genes. These genes make TRK proteins, which can help cancer cells grow.

Larotrectinib (Vitrakvi), and entrectinib (Rozlytrek), and repotrectinib (Augtyro) target and disable the abnormal TRK proteins made by the NTRK genes. Any of these drugs can be used in people with advanced thyroid cancer that has an NTRK gene change and is still growing despite other treatments.

These drugs are taken as pills or capsules, once or twice a day.

Common side effects of these drugs can include dizziness, fatigue, nausea, vomiting, constipation, weight gain, and diarrhea. Less common but more serious side effects can include liver damage, heart problems, confusion, and other nervous system problems.

For medullary thyroid cancer

Targeted drugs are important in treating advanced medullary thyroid cancer (MTC) because thyroid hormone-based treatments (including radioactive iodine therapy) are not effective against these cancers.

Multikinase inhibitors

Vandetanib (Caprelsa) and cabozantinib (Cometriq) are multikinase inhibitors (drugs that target several different kinase proteins). They can affect both cancer cells themselves and the growth of new blood vessels (which tumors need to grow). These drugs can be used to treat advanced MTC.

These drugs are taken as pills, typically once a day.

Common side effects of vandetanib include diarrhea, rash, nausea, high blood pressure, headache, fatigue, decreased appetite, and belly (abdominal) pain. Rarely, it can also cause serious or even life-threatening heart rhythm problems or infections. Because of its potential side effects, doctors must get special training before they are allowed to prescribe this drug.

Common side effects of cabozantinib include diarrhea, constipation, belly pain, mouth sores, decreased appetite, nausea, weight loss, fatigue, high blood pressure, loss of hair color, and hand-foot syndrome (redness, pain, and swelling of the hands and feet). Rarely, this drug can also cause serious side effects such as severe bleeding and holes in the intestine.

RET inhibitors

In some medullary thyroid cancers, the cells have certain changes in the RET gene that cause them to make an abnormal form of the RET kinase protein. This abnormal protein helps the cells grow.

Selpercatinib (Retevmo) is a type of drug known as a RET inhibitor. It works by attacking the RET protein. This drug can be used to treat advanced MTC if the cancer cells have certain types of RET gene changes.

This drug is taken by mouth as capsules or pills, typically twice a day.

Common side effects of selpercatinib can include dry mouth, diarrhea, constipation, high blood pressure, feeling tired, swelling in the hands or feet, skin rash, high blood sugar levels, low white blood cell or blood platelet counts, and changes in certain other blood tests.

Less common but more serious side effects can include liver damage, allergic reactions, changes in heart rhythm, bleeding easily, and problems with wound healing.

For anaplastic thyroid cancer

Anaplastic thyroid cancers are often hard to treat. If surgery can’t be done to remove the cancer, targeted drugs are often the preferred treatment if the cancer cells have certain gene changes. In some instances, giving a targeted drug first might shrink a tumor enough so that surgery can then be done.

BRAF and MEK inhibitors

Some anaplastic thyroid cancers have changes in the BRAF gene, which causes them to make certain proteins that can help them grow.

Dabrafenib (Tafinlar) and trametinib (Mekinist) are drugs that target some of these proteins. (Dabrafenib affects the BRAF protein, while trametinib targets the related MEK protein.) These drugs can be used together to treat anaplastic thyroid cancers that have a certain type of BRAF gene change and that can’t be removed completely with surgery.

These drugs are taken as pills or capsules each day.

Common side effects can include skin changes, rash, itching, sensitivity to the sun, headache, fever, chills, joint or muscle pain, fatigue, cough, hair loss, nausea, diarrhea, and high blood pressure.

Less common but serious side effects can include bleeding, heart rhythm problems, liver or kidney problems, lung problems, severe allergic reactions, severe skin or eye problems, and increased blood sugar levels.

Some people treated with these drugs develop skin cancers, especially squamous cell skin cancers. Your cancer care team will want to check your skin often during treatment. You should also let them know right away if you notice any new growths or abnormal areas on your skin.

RET inhibitors

In some anaplastic thyroid cancers, the cells have certain changes in the RET gene that cause them to make an abnormal from of the RET kinase protein. This abnormal protein helps the cells grow.

Selpercatinib (Retevmo) and pralsetinib (Gavreto) are drugs known as RET inhibitors. They work by attacking the RET protein. These drugs can be used to treat advanced anaplastic thyroid cancer if the cancer cells have certain types of RET gene changes.

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

Common side effects can include dry mouth, diarrhea, constipation, high blood pressure, feeling tired, swelling in the hands or feet, skin rash, high blood sugar levels, low white blood cell or blood platelet counts, and changes in certain other blood tests.

Less common but more serious side effects can include liver damage, allergic reactions, changes in heart rhythm, bleeding easily, and problems with wound healing.

TRK inhibitors

A small number of anaplastic thyroid cancers have changes in one of the NTRK genes. These genes make TRK proteins, which can help cancer cells grow.

Larotrectinib (Vitrakvi), entrectinib (Rozlytrek), and repotrectinib (Augtyro) target and disable the abnormal TRK proteins made by the NTRK genes. Any of these drugs can be used in people with anaplastic thyroid cancer that has an NTRK gene change and is still growing despite other treatments.

These drugs are taken as pills or capsules, once or twice a day.

Common side effects of these drugs can include dizziness, fatigue, nausea, vomiting, constipation, weight gain, and diarrhea. Less common but more serious side effects can include liver damage, heart problems, confusion, and other nervous system problems.