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Androgen blockers

Some salivary gland cancers, called androgen receptor positive tumors, grow in response to hormones. These are often high-grade tumors. Medications that block hormones might be used to treat them.

There are two categories of androgen blockers.

GNRH agonists lower hormone levels in the blood so there are not many hormones left to attach to the androgen receptors on the cancer cells. These include:

• Leuprolide (Lupron)
• Triptorelin (Trelstar Mixject, Triptodur)
• Goserelin (Zoladex)

Androgen receptor blockers block a protein on the cancer cells from responding to hormones. These include:

• Abiraterone (Abirtega)
• Bicalutamide (Casodex)
• Enzalutamide (Xtandi)

Sometimes these drugs might be used in combination, such as abiraterone and leuprolide.

Possible side effects

The most common side effects of these drugs are swelling, high blood pressure, changes in blood sugar, cholesterol or other blood tests, constipation, diarrhea, tiredness, and muscle or joint aches.

A severe but uncommon side effect of abiraterone is adrenocortical insufficiency, a life-threatening condition where the body does not respond well to stress or infection.

Abiraterone and bicalutamide can rarely cause severe liver injury or failure.

It is important to talk to your cancer care team about any side effects so that the medication can be changed or stopped if needed and symptoms can be treated.

Drugs that target HER2

HER2-positive salivary gland cancers make too much of a growth-promoting protein called HER2. If it is confirmed that the cancer is HER2-positive, drugs that target the HER2 protein might be helpful in treating these cancers.

Trastuzumab (Herceptin) is a monoclonal antibody that targets the HER2 protein. Trastuzumab is infused into a vein and can be given along with the chemotherapy drugs paclitaxel or docetaxel.

This drug is also used as an antibody-drug conjugate (ADC), where the antibody has been attached to chemo. These include:

• Ado-trastuzumab emtansine (Kadcyla or TDM-1)
• Fam-trastuzumab deruxtecan-nxki (Enhertu or T-DXd)

In this case, the anti-HER2 antibody acts like a homing signal by attaching to the HER2 protein on cancer cells, bringing the chemo directly to them. These drugs are given in a vein intravenously (IV).

Possible side effects

Common side effects of ADC HER2 drugs include swelling, hair loss, decreased appetite, changes in bowel habits, nausea, vomiting, low blood counts, and muscle or joint pains.

Serious side effects of HER2-targeted drug therapy can include heart or lung damage and infections.

It is important to talk to your cancer care team about any side effects so that the medication can be changed or stopped if needed and symptoms can be treated.

Drugs that target TRK proteins

Some salivary gland cancers have changes in one of the NTRK genes. These gene changes cause them to make abnormal TRK proteins, which can lead to abnormal cell growth and cancer. This gene change is more often seen in secretory salivary gland cancers.

Larotrectinib (Vitrakvi), repotrectinib (Augtyro), and entrectinib (Rozlytrek) are drugs that target the TRK proteins. These drugs can be used first to treat advanced salivary gland cancers with NTRK gene changes.

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

Possible side effects

Common side effects of TRK inhibitors include swelling, skin rashes, changes in bowel habits, nausea, vomiting, changes in appetite, low blood cell counts, liver damage, muscle and joint pain, fragile bones, cough, fever, and dizziness (especially with repotrectinib).

It is important to talk to your cancer care team about any side effects so that the medication can be changed or stopped if needed and symptoms can be treated.

Drugs that target RET

Some salivary gland cancers have changes in the RET genes. These gene changes cause them to make abnormal RET proteins, which signal cancer cells to grow and divide. Selpercatinib (Retevmo), a RET inhibitor, helps block cancers with these changes from growing.

This drug is given as a tablet or capsule by mouth twice a day.

Possible side effects

Common side effects of selpercatinib include swelling, high blood pressure, skin rash, changes in blood test results (such as blood sugar, liver and kidney tests, and cholesterol), belly pain, changes in bowel habits, nausea, vomiting, low blood counts, tiredness, and muscle or joint pain.

Serious but rare side effects include heart or lung injury, bleeding, or life-threatening high blood pressure.

It is important to talk to your cancer care team about any side effects so that the medication can be changed or stopped if needed and symptoms can be treated.

Drugs that target BRAF

Some salivary gland cancers have changes in the BRAF gene. This gene change can lead to uncontrolled cancer cell growth. Dabrafenib (Tafinlar), helps block cell growth in tumors with these gene changes. It is often given in combination with another drug called trametinib (Mekinist), a drug that blocks another protein in the growth signal pathway.

This drug is given as a tablet or capsule by mouth twice a day. Trametinib is also given by mouth as a tablet or liquid solution.

Possible side effects

Common side effects of dabrafenib include hair loss, palmar-plantar erythrodysesthesia (a red, painful rash of the palms and soles), high blood sugar, chills, headache, muscle or joint pains, and cough.

In rare cases, dabrafenib can cause severe skin reactions or heart problems. These are often reversible by stopping or lowering the dose of the drug.

It is important to talk to your cancer care team about any side effects so that the medication can be changed or stopped if needed and symptoms can be treated.

Drugs that target FGFR

Some cancers have gene changes in FGFR. When this happens, cells lose the ability to stop growing and dividing, leading to uncontrolled growth. Erdafitinib (Balversa) is a tyrosine kinase inhibitor (TKI) that targets FGFR protein receptors and helps block cancer growth.

This drug is given as a tablet once a day.

Possible side effects

Common side effects of erdafitinib include hair and nail changes, palmar-plantar erythrodysesthesia, changes in bowel habits, decreased appetite, nausea, vomiting, low blood counts, changes in liver and kidney blood tests, tiredness, changes in vision, and dry eyes.

It is important to talk to your cancer care team about any side effects so that the medication can be changed or stopped if needed and symptoms can be treated.

Drugs that target blood vessel growth

Vascular endothelial growth factor (VEGF) is a protein that helps tumors form new blood vessels, a process known as angiogenesis. VEGF can be an important driver for some salivary gland cancers, such as adenoid cystic carcinoma (ACC). VEGF helps the tumor get the nutrients it needs to grow.

Axitinib (Inlyta), Lenvatinib (Lenvima), and sorafenib (Nexavar) are drugs called TKIs, which block VEGF. Some of these drugs block other growth signals as well.

Possible side effects

Common side effects from these drugs include high blood pressure, palmar-plantar erythrodysesthesia, belly pain, changes in bowel habits, nausea, vomiting, low blood counts, changes in liver and kidney blood tests, low thyroid hormone levels, headache, joint pain, and cough.

Severe but rare side effects might include heart or liver problems, bleeding, blood clots, severe high blood pressure, or damage to the intestines.

It is important to talk to your cancer care team about any side effects so that the medication can be changed or stopped if needed and symptoms can be treated.