Targeted Drug Therapy for Ovarian Cancer

Targeted therapy is a type of cancer treatment that uses drugs to attack parts of cancer cells that make them different from normal, healthy 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.

Bevacizumab

Bevacizumab (Avastin, other names) belongs to a class of drugs called angiogenesis inhibitors. For cancers to grow and spread, they need to make new blood vessels to nourish themselves (called angiogenesis). This drug attaches to a protein called VEGF (that signals new blood vessels to form) and slows or stops cancer growth.

Bevacizumab 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. But it doesn’t seem to help women live longer.

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

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

Side effects of bevacizumab

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

Rare but possibly serious side effects can include blood clots, severe bleeding, slow wound healing, holes forming in the colon (called perforations), and the formation of abnormal connections between the bowel and the skin or bladder (fistulas). If a perforation or fistula occurs it can lead to severe infection and may require surgery to correct.

PARP inhibitors

Olaparib (Lynparza), rucaparib (Rubraca), and niraparib (Zejula) are drugs known as a PARP (poly(ADP)-ribose polymerase) inhibitors. PARP enzymes normally help repair damaged DNA inside cells. The proteins made by the BRCA genes (BRCA1 and BRCA2) also normally help repair DNA, but in a different way. Mutations in BRCA genes can make it hard for a cell to repair its DNA. PARP inhibitors can make it even harder for tumor cells with an abnormal BRCA gene to repair damaged DNA, which often leads to the death of these cells.

If you are not known to have a BRCA mutation, your doctor might test your blood or saliva and your tumor to be sure you have one 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. This drug can be used in patients with or without mutations in one of the BRCA genes.

In women with a BRCA mutation:

• Olaparib can be used as maintenance treatment for advanced ovarian cancer that has gotten smaller in response to first treatment with chemotherapy containing cisplatin or carboplatin.
• Olaparib can be used with bevacizumab (see above) as maintenance treatment in women whose cancers have shrunk quite a bit with chemotherapy containing carboplatin or cisplatin.

In women without a BRCA mutation:

• If the tumor has a high genomic instability score (a test measuring the amount of abnormal genes in cancer cells), olaparib can be used with bevacizumab as maintenance treatment in women whose cancers have shrunk quite a bit with chemotherapy containing carboplatin or cisplatin.

In women with or without a BRCA mutation:

• Olaparib can be used as maintenance treatment for advanced ovarian cancer that has come back after treatment, and then has 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:

• Niraparib might be used as maintenance treatment for advanced ovarian cancer, where the cancer has shrunk with first-line chemotherapy containing cisplatin or carboplatin.

In women with a BRCA gene mutation:

• Niraparib might be used as maintenance treatment for advanced ovarian cancer that has come back after treatment, where the cancer 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 then has shrunk in response to chemotherapy containing cisplatin or carboplatin.

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.

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 patients 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 linked to a chemotherapy drug. Once it's in the body, 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 that 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 of this drug 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 cells with NTRK gene changes

A very small number of ovarian cancers have changes in one of the NTRK genes. Cells with these gene changes can lead to abnormal cell growth and cancer. Larotrectinib (Vitrakvi) and entrectinib (Rozlytrek) are targeted drugs that stop the proteins made by the abnormal NTRK genes. These drugs can be used in people with advanced ovarian cancer whose tumor has an NTRK gene change and is still growing despite other treatments.

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

Side effects of drugs that target NTRK gene changes

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

Less common but serious side effects can include abnormal liver tests, heart problems, and confusion.