Targeted Therapy Drugs for Brain Tumors in Children

Targeted therapy drugs treat cancer by targeting specific changes or features in cancer cells. These drugs work in different ways. They can be used instead of or along with chemo in some situations, and they have side effects that are different from chemo. Some targeted drugs can be useful in brain tumors.

The gene changes present in a tumor determine whether these treatments are a good choice. Certain gene changes are more common in some types of brain tumors, and some can happen in many kinds of cancer. Knowing which gene changes are present is the most important information doctors use to decide whether a targeted drug may work for your (child’s) tumor.

Drugs that target BRAF gene changes

Some tumor cells have changes (mutations) in the BRAF gene, which cause them to make certain proteins that help the cells grow. These changes are more common in low grade gliomas.

Drugs that target BRAF gene mutations include:

• Dabrafenib (Tafinlar)
• Vemurafenib (Zelboraf)
• Tovorafenib (Ojemda)

Drugs that target the MEK protein (related to how BRAF works) include:

• Trametinib (Mekinist)
• Selumetinib (Koselugo)

These drugs are typically taken once or twice a day as a liquid or pill/capsule.

Possible side effects

The most common side effects of these types of drugs include:

• Skin reactions, such as a rash, a sunburn-type reaction with exposure to sunlight, or a rash on the palms of the hands and soles of the feet
• Swelling or weight gain
• Hair changes, including hair loss and changes in color or texture
• Joint pain
• Fatigue or low energy
• Fevers
• Diarrhea, constipation, or low appetite
• High blood sugar

These medications can cause heart problems, so the heart may be monitored during treatment. Children who receive tovorafenib may experience slowed growth while on the treatment, which will be monitored. However, when the treatment is stopped, they tend to catch up to their expected height.

Some people treated with these drugs have developed skin cancers, especially squamous cell skin cancers. In rare cases, severe and life-threatening skin rashes called Stevens-Johnson syndrome and toxic epidermal necrolysis have also been seen. Your cancer care team will want to check the skin often during treatment. You should also let them know right away if you notice any new growths or abnormal areas on the skin.

Drugs that target IDH gene changes

In 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 seem to help the tumor cells mature into more normal cells.

This drug can be used after surgery in people 12 years of age and older with a grade 2 astrocytoma or oligodendroglioma if the tumor cells have an IDH1 or IDH2 gene mutation. The doctor can get tests of the tumor cells to see whether they have one of these mutations.

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

Side effects

Common side effects of vorasidenib can include:

• Fatigue or low energy
• Headaches
• Nausea
• Muscle aches or stiffness
• Diarrhea
• Seizures
• Elevated liver blood tests

Sometimes this drug can 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 cancer care team know if any of these symptoms appear.

Drugs that target H3 K27M gene changes

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

Dordaviprone (Modeyso)

Dordaviprone is a type of targeted drug known as a protease activator. It seems to work by helping to restore more normal gene function within the cells.

Dordaviprone can be used to treat tumors with an H3 K27M mutation if the tumor is still growing after another treatment has been tried.

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

Side effects of dordaviprone can include:

• Fatigue or low energy
• Headache
• Nausea and vomiting
• Muscle, joint, or bone pain
• Low blood cell counts
• Liver damage

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 NTRK gene changes

NTRK gene changes in tumors tend to promote cell growth and division. Drugs that block NTRK work to control the growth of tumors.

Drugs that target NTRK gene changes include:

• Larotrectinib (Vitrakvi)
• Entrectinib (Rozlytrek)
• Repotrectinib (Augtyro)

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

Side effects

Side effects of these drugs can include:

• Swelling of the body
• Skin rashes
• Nausea and vomiting
• Changes in appetite and weight
• Constipation
• Low blood cell counts
• Liver damage
• Muscle and joint pain
• Broken or fragile bones
• Cough
• Fever
• Dizziness (especially with repotrectinib)

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

Drugs that target ALK gene changes

Drugs that target ALK gene changes are in a class of drugs called tyrosine kinase inhibitors (TKIs). These drugs work by blocking the signals cells need to grow and divide. Examples of TKIs that target ALK gene changes include:

• Lorlatinib (Lorbrena)
• Alectinib (Alecensa)

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

Side effects

Side effects of these drugs can include:

• Swelling of the body
• High cholesterol
• High blood sugar
• Nausea or vomiting
• Diarrhea or constipation
• Low blood cell counts
• Liver damage
• Low energy
• Headaches
• Trouble sleeping or remembering things (more common with lorlatinib)
• Muscle or joint pain

Less common but serious side effects can include:

• A serious problem with the lungs called pneumonitis (more common with alectinib, but still rare)

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

Drugs that target the SHH pathway

Vismodegib (Erivedge)

The sonic hedgehog (SHH) pathway is a group of signals that help control how cells grow and develop. Changes in genes that are part of this pathway can cause tumor cells to grow and divide quickly. Vismodegib blocks signaling in the SHH pathway, slowing cell growth.

This drug has worked in some young adults with medulloblastoma with SHH pathway-related gene changes. It is now being studied for use in younger people with medulloblastoma.

This drug is given as a capsule once a day.

Side effects

Common side effects of vismodegib include:

• Hair loss
• Low appetite
• Low energy
• Nausea or vomiting
• Diarrhea or constipation
• Muscle spasms or pain

In children, premature closure of the growth plates has been seen, so the drug is usually avoided in children who are still growing.

Rare, more serious side effects include severe skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis. Vismodegib causes birth defects and cannot be given during pregnancy.

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

mTOR inhibitors

mTOR inhibitors work by blocking a cell protein known as mTOR, which normally helps cells grow and divide into new cells. mTOR inhibitors can be used for a specific type of brain tumor called a subependymal giant cell astrocytoma (SEGA), which is more common in people with tuberous sclerosis, when it cannot be completely removed with surgery. mTOR inhibitors include:

• Everolimus
• Sirolimus

These drugs are usually given as a tablet or liquid once a day.

Side effects

Common side effects can include:

• Fatigue or low energy
• Mouth sores
• Increased risk of infections
• Nausea or vomiting and low appetite
• Diarrhea
• Skin rash
• Fluid buildup, usually in the legs
• High blood sugar
• High cholesterol levels

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

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

Drugs that target angiogenesis (blood vessel growth)

Bevacizumab (Avastin) works by blocking a protein called vascular endothelial growth factor (VEGF). VEGF helps tumors form new blood vessels (a process called angiogenesis).  Without a blood supply, tumors have trouble growing and dividing. This drug can be used to treat some gliomas.

This drug is given as an infusion through an intravenous (IV) line.

Side effects

Side effects of bevacizumab can include:

• High blood pressure
• Swelling of the body
• Nausea or vomiting
• Constipation
• Low appetite
• Low blood cell counts
• Muscle or joint pain
• Blood clots or bleeding
• Kidney problems

This drug can cause problems with healing after surgery, so it is usually avoided for about a month before and after surgery.

Serious side effects of bevacizumab can include infusion reactions (similar to an allergic reaction), ulcers or damage to the stomach and intestines, severe bleeding or life-threatening clots, and heart and kidney problems.

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