Targeted Drug Therapy for Brain Tumors in Adults

Targeted therapy drugs treat cancer by targeting specific changes or features in cancer cells. These drugs work in different ways.

Some targeted drugs might be helpful for certain types of brain or spinal cord tumors. More are being studied in clinical trials.

Drugs that target angiogenesis (blood vessel growth)

Bevacizumab (Avastin and other brand names) works by blocking a protein called vascular endothelial growth factor (VEGF). VEGF helps tumors form new blood vessels (a process called angiogenesis), which they need to grow.

This drug is used mainly to treat some types of fast-growing gliomas such as glioblastomas. It might also be useful in treating some other types of tumors, such as meningiomas.

Bevacizumab can help shrink some tumors or slow their growth, especially when combined with chemotherapy. Its main benefit is that it helps reduce swelling around the tumor, so people getting it can often get lower doses of the steroid dexamethasone. This can be especially important for people sensitive to steroid side effects.

Bevacizumab is given by intravenous (IV) infusion, usually once every 2 weeks.

Side effects of bevacizumab

Common side effects include high blood pressure, tiredness, bleeding, low white blood cell counts, headaches, mouth sores, loss of appetite, and diarrhea.

Less common but possibly serious side effects include blood clots, internal bleeding, heart problems, and holes (perforations) in the intestines.

This drug can also slow wound healing, so usually it can't be given within a few weeks of surgery.

Drugs that target tumors with IDH gene changes

In people with some types of brain tumors, the tumor cells might have a change (mutation) in either the IDH1 or IDH2 gene. These genes help the cells make proteins also called IDH1 and IDH2. Mutations in one of these genes can stop the tumor cells from maturing the way they normally would.

Vorasidenib (Voranigo) is a type of targeted drug known as an IDH inhibitor. It blocks abnormal IDH1 and IDH2 proteins, which seems to help the tumor cells mature into more normal cells.

This drug can be used after surgery in people with a grade 2 astrocytoma or oligodendroglioma and possibly some other tumors, if the tumor cells are found to have an IDH1 or IDH2 gene mutation. Your doctor can test your tumor cells to see if they have one of these mutations.

This drug is taken by mouth as tablets, typically once a day.

Side effects of vorasidenib

Common side effects include feeling very tired, headache, nausea, muscle aches or stiffness, diarrhea, seizures, and changes in lab tests showing the drug is affecting the liver.

Sometimes this drug might have more serious effects on the liver, which could lead to symptoms such as jaundice (yellowing of the eyes and skin), dark urine, loss of appetite, or pain in the upper right side of your belly. It’s important to let your health care team know if you have any of these symptoms.

Drugs that target tumors with H3 K27M changes

Brain tumors known as diffuse midline gliomas often have a genetic change known as an H3 K27M mutation, which affects how some genes in the cell work.

Dordaviprone (Modeyso) is a type of targeted drug known as a protease activator. It seems to work by helping to restore more normal gene control within the cell.

Dordaviprone can be used to treat diffuse midline gliomas that have the H3 K27M mutation, if the tumor is still growing despite prior treatment.

This drug is taken by mouth, typically once a week. It can be taken as capsules, or the contents of the capsules can be dissolved into a liquid.

Side effects of dordaviprone

Common side effects include feeling very tired, headache, nausea and vomiting, and muscle, joint, and bone pain. It can also lower your blood cell counts and lead to changes in lab tests showing the drug is affecting the liver.

Less common but more serious side effects can include:

• Allergic reactions, which can show up as hives, skin rash, fever, feeling faint or dizzy, wheezing or trouble breathing, or swelling of the face or throat
• Heart rhythm problems, which might show up as symptoms like feeling lightheaded or faint, feeling dizzy, having heart palpitations or a fast heartbeat, or shortness of breath

Drugs that target mTOR

Everolimus (Afinitor) is a type of targeted drug known as an mTOR inhibitor. It works by blocking the mTOR protein, which normally helps cells grow and divide into new cells.

This drug may be used to treat subependymal giant cell astrocytomas (SEGAs) that can’t be removed completely by surgery. It may shrink the tumor or slow its growth for some time, although it’s not clear if it can help people with these tumors live longer.

Everolimus is taken as a pill, typically once a day.

Side effects of everolimus

Common side effects of everolimus include mouth sores, increased risk of infections, nausea, loss of appetite, diarrhea, skin rash, feeling tired or weak, fluid buildup (usually in the legs), and increases in blood sugar and cholesterol levels.

A less common but serious side effect is damage to the lungs, which can cause shortness of breath or other problems.

Drugs that target tumors with BRAF gene changes

Some tumors have changes in the BRAF gene, which causes them to make an altered BRAF protein that helps them grow.

Drugs that target the BRAF protein (known as BRAF inhibitors) or the related MEK protein (known as MEK inhibitors) might be an option to treat these tumors, typically after other treatments have been tried. Examples include:

• Dabrafenib (Tafinlar) plus trametinib (Mekinist)
• Vemurafenib (Zelboraf) plus cobimetinib (Cotellic)
• Tovorafenib (Ojemda)

These drugs are taken as pills or capsules each day. Tovorafenib can also be taken as a liquid.

Side effects of BRAF and MEK inhibitors

Common side effects 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 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.

Drugs that target tumors with NTRK gene changes

In a small number of brain tumors, the cells have changes in one of the NTRK genes. This causes them to make abnormal TRK proteins, which can help tumor cells grow.

Larotrectinib (Vitrakvi), entrectinib (Rozlytrek), and repotrectinib (Augtyro) are drugs that target the TRK proteins, so they are called TRK inhibitors. These drugs can be used to treat tumors with NTRK gene changes that are still growing despite other treatments.

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

Side effects of TRK inhibitors

Common side effects include dizziness, fatigue, nausea, vomiting, constipation, weight gain, and diarrhea.

Less common but serious side effects include abnormal liver tests, increased risk for fractures, heart problems, vision changes, and confusion.