Targeted Therapy Drugs for Brain and Spinal Cord Tumors in Children

Drugs that target tumors with BRAF gene changes

In some low-grade gliomas, the tumor cells have changes (mutations) in the BRAF gene, which causes them to make certain proteins that help the cells grow.

Dabrafenib (Tafinlar) and trametinib (Mekinist)

Dabrafenib and trametinib are targeted drugs that affect some of these proteins. (Dabrafenib targets the BRAF protein, while trametinib affects the related MEK protein.) Combining these drugs might be an option for children at least one year of age with any type of low-grade glioma with a BRAF V600E mutation that needs treatment other than surgery or radiation. If your child has a low-grade glioma, the tumor cells might be tested for this gene change to see if these drugs might be helpful.

These drugs are typically taken daily, either as pills or as liquids.

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 have developed skin cancers, especially squamous cell skin cancers. Your child’s doctor will want to check their skin often during treatment. You should also let the doctor know right away if you notice any new growths or abnormal areas on your child’s skin.

Tovorafenib (Ojemda)

Tovorafenib targets the BRAF protein. This drug might be an option for children at least 6 months of age with any type of low-grade glioma that has a BRAF gene change and that has come back or is no longer responding to other treatments. If your child has a low-grade glioma, the tumor cells might be tested for BRAF gene changes to see if this drug might be helpful.

This drug is typically taken once a week, either as pills or as a liquid.

Common side effects of tovorafenib can include skin changes (such as rash, dry skin, or acne), sensitivity to the sun, hair color changes, feeling tired, headache, nausea and vomiting, fever, constipation, an increased risk of infections, and changes in some blood test results. This drug might also slow a child’s growth.

Less common but serious side effects can include serious bleeding, liver problems, and severe reactions to sunlight.

Drugs that target tumors with IDH gene changes

In children 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 certain proteins, which are 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)

Vorasidenib 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 children 12 years of age and older with a grade 2 astrocytoma or oligodendroglioma, if the tumor cells are found to have an IDH1 or IDH2 gene mutation. The doctor can get tests of the tumor cells to see if they have one of these mutations.

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

Common side effects of vorasidenib can 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 the belly. It’s important to let the health care team know if any of these symptoms appear.

Everolimus (Afinitor)

For subependymal giant cell astrocytomas (SEGAs) that can’t be removed completely by surgery, everolimus may shrink the tumor or slow its growth for some time. This drug works by blocking a cell protein known as mTOR, which normally helps cells grow and divide into new cells.

Everolimus is a pill taken once a day.

Common side effects of everolimus can 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 lung damage, which can cause shortness of breath or other problems.

Many other targeted drugs are now being developed and studied in clinical trials. Some of these are described in What’s New in Research and Treatment for Brain and Spinal Cord Tumors in Children?