Targeted Drug Therapy for Salivary Gland Cancer

Targeted drug therapy uses medicines that target or are directed at proteins on cancer cells that help them grow, spread, and live longer. Recent research has shown that some salivary gland cancers make certain proteins or have gene changes that can be targeted with specific drugs to destroy cancer cells or slow their growth. Many of these drugs can be taken as pills and their side effects are different from those of chemotherapy (sometimes less severe).

Some targeted drugs, for example, monoclonal antibodies, work in more than one way to control cancer cells and may also be considered immunotherapy because they boost the immune system.

Drugs that target the androgen receptor

Hormone therapy is a common treatment for prostate cancers and breast cancers and it has been found to be helpful in certain salivary gland cancers, too.

Some salivary gland cancers make a protein called an androgen receptor that helps cancer cells grow with hormones. Bicalutamide (Casodex) is a hormone drug (given as a pill) that attaches to this receptor (protein) to keep the cancer from growing. It is typically given with leuprolide (Lupron, Eligard), another type of hormone therapy, that lowers the hormone levels in the blood so there are not many hormones left to attach to the androgen receptor. This also makes it hard for the cancer to grow. Leuprolide is injected or placed as small implants under the skin. To use this combined treatment, salivary gland cancers must be tested first in the lab for the androgen receptor. This hormone treatment is often given after chemotherapy has been tried.

Side effects of bicalutamide and leuprolide given together can include diarrhea, feeling sick to your stomach, liver problems, and tiredness.

Drugs that target HER2

Some salivary gland cancers make too much of a growth-promoting protein called HER2. Cancers with high levels of HER2 are called HER2-positive. Drugs that target the HER2 protein can often be helpful in treating these cancers, specifically mucoepidermoid and salivary ductal carcinomas.

Trastuzumab (Herceptin) is a monoclonal antibody, a man-made version of an immune system protein, which targets the HER2 protein. This drug only works if the cancer cells have too much HER2 protein, so they must be tested for HER2 before starting treatment. Trastuzumab is infused into a vein and is usually given along with paclitaxel or docetaxel (chemotherapy drugs).

If trastuzumab and a taxane chemotherapy combination has been tried and is no longer working, sometimes an antibody-drug conjugate (ADC) might be used. An ADC is a monoclonal antibody linked to a chemotherapy drug. 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. Ado-trastuzumab emtansine (Kadcyla or TDM-1), an ADC, has had favorable initial results in salivary gland cancers that are HER2 positive. This drug is given in a vein (IV).

Serious side effects of HER2 targeted drug therapy can include heart damage or heart failure.

TRK inhibitors

Some salivary gland cancers have changes in one of the NTRK genes. This gene change causes 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) 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.

Common side effects of TRK inhibitors include muscle and joint pain, cough, dizziness, fatigue, nausea, vomiting, constipation, fever, abdominal pain, and diarrhea.