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Targeted therapy drugs treat cancer by targeting specific features, changes, mutations, or substances in or on cancer cells. Each type of targeted therapy works differently, but they all change the way a cancer cell grows, divides, repairs itself, or interacts with other cells.

Angiogenesis inhibitors

How they work (mechanism of action): To get the blood and nutrients they need to grow, tumors send signals that cause new blood vessels to form nearby. This process is called angiogenesis. Angiogenesis inhibitors help stop the formation of new blood vessels.

Some of the most common angiogenesis inhibitors target the vascular endothelial growth factor protein (VEGF), so they are called VEGF inhibitors. They are a type of monoclonal antibody, which is a lab-made version of a specific immune system protein.

Bevacizumab (Avastin) is a VEGF inhibitor that has been shown to shrink or slow the growth of advanced epithelial ovarian cancers. Bevacizumab appears to work even better when given along with chemotherapy having shown good results in terms of shrinking (or stopping the growth of) tumors. However, it doesn’t seem to help women live longer.

Bevacizumab can also be given with olaparib (see below) as maintenance treatment for cancers with a BRCA gene mutation or genomic instability (see below) that have shrunk quite a bit with chemotherapy containing carboplatin or cisplatin.

Bevacizumab is given as an infusion into the vein (IV) every 2 to 3 weeks.

Side effects of angiogenesis inhibitors

• Common side effects: Nosebleed, headache, high blood pressure, protein in urine, change in taste, dry skin, back pain, dry skin, excessive tearing
• Rare, but serious side effects: Severe bleeding, formation of holes (perforations) in the intestine, issues with wound healing, clots in the heart and/or brain, and brain damage called reversible posterior leukoencephalopathy syndrome (RPLS), very high blood pressure, kidney damage, allergic reaction to the drug (infusion reaction), thyroid damage, ovarian failure, and fetal harm.

Because of the risks of bleeding, these drugs often aren’t used in people who are coughing up blood or taking blood thinners.

Learn more: Angiogenesis Inhibitors

PARP inhibitors

Olaparib (Lynparza), rucaparib (Rubraca), and niraparib (Zejula) are PARP inhibitors. They block an enzyme called PARP (poly[ADP]-ribose polymerase), which normally helps repair damaged DNA inside cells.

The BRCA genes (BRCA1 and BRCA2) also make proteins that help repair DNA, but in a different way. When these genes are mutated, cancer cells may have trouble fixing DNA damage. PARP inhibitors can make it even harder for these cells to repair damaged DNA, which often leads to their death.

These drugs have been shown to help shrink or slow the growth of some advanced ovarian cancers for a time. So far, though, it's not clear if they can help women live longer.

If you are not known to have a BRCA mutation, your doctor might test your blood or saliva and your tumor before starting treatment with one of these drugs.

All of these drugs are taken daily by mouth, as pills or capsules.

Olaparib (Lynparza) is used to treat advanced ovarian cancer, typically after chemotherapy has been tried. It can be used in people with or without a BRCA mutation.

In women with a BRCA mutation, olaparib can be used:

• As maintenance treatment for advanced cancer, if the cancer has gotten smaller after first-line chemotherapy (cisplatin or carboplatin)
• With bevacizumab as maintenance treatment if the cancer has shrunk quite a bit with chemotherapy containing carboplatin or cisplatin
• As maintenance treatment for advanced cancer that has come back after treatment and has then shrunk in response to chemotherapy containing cisplatin or carboplatin

In women without a BRCA mutation, olaparib can be used:

• With bevacizumab as maintenance treatment if the tumor has a high genomic instability score (a test measuring the amount of abnormal genes in cancer cells) and has shrunk quite a bit with chemotherapy containing carboplatin or cisplatin
• As maintenance treatment for advanced cancer that has come back after treatment and has then shrunk in response to chemotherapy containing cisplatin or carboplatin

Niraparib (Zejula) may be used in some situations to treat ovarian cancer in women with or without a BRCA gene mutation:

• As maintenance treatment for advanced ovarian cancer if it has shrunk with first-line chemotherapy (cisplatin or carboplatin)

In women with a BRCA gene mutation, niraparib might also be used:

• As maintenance treatment for advanced ovarian cancer that has come back after treatment and has then shrunk with chemotherapy containing cisplatin or carboplatin.

Rucaparib (Rubraca) can be used in women with or without a BRCA mutation, as maintenance treatment for advanced ovarian cancer that has come back after treatment and has then shrunk in response to chemotherapy containing cisplatin or carboplatin.

Side effects of PARP inhibitors

Side effects of these drugs can include nausea, vomiting, diarrhea, fatigue, loss of appetite, taste changes, low red blood cell counts (anemia), belly pain, and muscle and joint pain.

Rarely, some people treated with these drugs have developed a blood cancer, such as myelodysplastic syndrome or acute myeloid leukemia.

Drugs that target folate receptor-alpha

In many ovarian cancers, the cells have high levels of the folate receptor-alpha (FR-alpha) protein on their surfaces. Drugs that target this protein might be an option to treat these cancers.

Mirvetuximab soravtansine (Elahere) is an antibody-drug conjugate (ADC), which is a lab-made antibody attached to a chemotherapy drug. The antibody acts like a homing device by attaching to the FR-alpha protein on cancer cells, which brings the chemo directly to them.

This drug can be used to treat epithelial ovarian cancer that tests positive for FR-alpha and is no longer responding to platinum chemotherapy drugs such as cisplatin or carboplatin.

This drug is infused into a vein (through an IV line or central venous catheter), typically once every 3 weeks. Before each treatment, you’ll get medicines to help prevent infusion reactions, nausea, and vomiting.

Side effects of mirvetuximab soravtansine

Common side effects can include nausea and vomiting, diarrhea or constipation, feeling tired, belly pain, low blood cell counts, and changes in mineral levels in the blood.

This drug can cause eye problems, which can sometimes be serious. Problems can include blurred vision, dry eyes, light sensitivity, eye pain, or vision changes. You’ll need an eye exam before being treated with this drug, and your doctor will prescribe eye drops for you to use before and during your treatment. Tell your doctor or nurse right away if you develop any eye problems.

This drug can cause serious lung disease in some people, which might even be life threatening. It’s very important to let your doctor or nurse know right away if you’re having symptoms such as coughing, trouble breathing, or chest pain.

This drug can also cause nerve damage (peripheral neuropathy), which can lead to numbness, tingling, or weakness in the hands or feet.

Drugs that target NTRK gene changes

How they work (mechanism of action): A very small number of ovarian cancers have changes in one of the NTRK genes, called NTRK gene fusions. Cells with these gene changes make abnormal TRK proteins, which can lead to abnormal cell growth and cancer. NTRK inhibitors target and disable the proteins made by the NTRK genes.

Larotrectinib (Vitrakvi), entrectinib (Rozlytrek), and repotrectinib (Augtyro) are NTRK inhibitors.

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

Side effects of TRK inhibitors

• Common side effects: Abnormal liver tests, low white and red blood cell counts, muscle and joint pain, tiredness, diarrhea or constipation, nausea and vomiting, and stomach pain.
• Rare, but serious side effects: Mental changes, such as confusion, changes in mood, changes in sleep; liver damage; changes in heart rhythm and/or function; vision changes; and harm to a fetus.

Drugs that target BRAF gene changes

How they work (mechanism of action): Some ovarian cancers have changes in the BRAF gene. Cells with these changes make an altered BRAF protein that helps them grow. BRAF inhibitors target this and related proteins.

A combination of the BRAF inhibitor Dabrafenib (Tafinlar) and another drug called trametinib (Mekinist) (a type of MEK inhibitor) is often given for advanced cancer with the BRAF V600E mutation.

These drugs are taken as pills or capsules each day.

Side effects of BRAF inhibitors

• Common side effects: Skin thickening, rash, itching, sensitivity to the sun, headache, fever, joint pain, tiredness, hair loss, nausea, and diarrhea.
• Rare, but serious side effects: Bleeding, heart rhythm problems, liver or kidney problems, lung problems, severe allergic reactions, severe skin or eye problems, increased blood sugar levels, and squamous cell skin cancer.

Drugs that target HER2 gene changes

How they work (mechanism of action): In a small percentage of ovarian cancer, the cancer cells have certain changes in the HER2 (ERBB2) gene that help them grow. HER2-directed drugs can be used to treat metastatic ovarian cancer if the cancer cells have certain types of HER2 gene changes.

Fam-trastuzumab deruxtecan (Enhertu) is an antibody-drug conjugate (ADC). It’s made up of a lab-made antibody that targets the HER2 protein attached to a chemotherapy drug. The antibody acts like a homing device by attaching to the HER2 protein on cancer cells, bringing the chemo directly to them.

These drugs are infused into a vein (IV). They are typically given once every few weeks.

Side effects of HER2 inhibitors

• Common side effects: Low white blood cell, red blood cell, and platelet counts; tiredness; hair loss; nausea and vomiting; muscle and joint pain; and changes in other blood tests.
• Rare, but serious side effects: Changes in heart function and a severely low white blood cell count, which increases your risk of infection.

Drugs that target RET gene changes

How they work (mechanism of action): In a small percentage of ovarian cancers, the tumor cells have rearrangement in the RET gene that causes them to make an abnormal form of the RET protein. This abnormal protein helps the tumor cells grow. RET inhibitors can be used to treat advanced cancers with the RET rearrangement.

These drugs are taken by mouth as capsules, typically once or twice a day.

Selpercatbinib is a RET inhibitor. Side effects include:

• Common side effects: Dry mouth, diarrhea or constipation, high blood pressure, tiredness, swelling in hands and/or feet, skin rash, muscle and joint pain, and low blood cell counts or changes in other blood tests.
• Rare, but serious side effects: Liver damage, lung damage, allergic reactions, changes in heart rhythm, bleeding easily, and problems with wound healing.

Drugs that target KRAS gene changes

How they work (mechanism of action): Some ovarian cancers have changes in the KRAS gene that cause them to make an abnormal form of the KRAS protein. This abnormal protein helps the cancer cells grow and spread.

The combination of Avutometinib (RAF/MEK inhibitor) and Defactinib (FAK inhibitor) can be effective in treating low-grade serous ovarian cancer with KRAS gene changes. This drug combination is known as the Avmapki Fakzynja Co-Pack.

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

Side effects of the Avutometinib and Defactinib drug combination:

• Common side effects: nausea, diarrhea, vomiting, abdominal pain, fatigue, muscle/joint pain, swelling, urinary tract infection, and laboratory changes involving the liver and blood cell count.
• Rare, but serious side effects: Vision changes, rashes, liver damage, muscle damage, and fetal harm.