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PARP inhibitors

This page was reviewed under our medical and editorial policy by

Ruchi Garg, MD, CTCA Program Director, Gynecologic Oncology.

This page was reviewed on March 30, 2022.

PARP, or poly (ADP-ribose) polymerase, is a protein that helps your cells repair themselves. Cancer cells and healthy cells contain genetic information called DNA that sometimes becomes damaged. Unrepaired DNA prevents cells from dividing and multiplying, resulting in cell death. To fix DNA damage and stay alive, some types of cancer cells use PARP as part of a process called homologous recombination DNA damage repair (HR-DDR).

PARP inhibitors are drugs that block the DNA-repairing mechanism of PARP. By preventing PARP from repairing the damaged DNA within cancer cells, PARP inhibitors can help kill them. These drugs fall under the category of targeted therapies because they block a specific repair mechanism within cancer cells, which helps to destroy them or prevent their growth.

PARP inhibitors may be a treatment option for certain stages and types of ovarian cancer, pancreatic cancer and prostate cancer, diseases that harbor HR-DDR mutations. For example, many ovarian tumors already have mutations that hinder the ability to repair DNA with certain gene mutations, such as BRCA, which is one of the most well-known HR-DDR mutations. For example, about 10 percent of women with ovarian cancer have mutations in the BRCA1 and BRCA2 genes, according to the Centers for Disease Control and Prevention. BRCA and other similar mutations are estimated to be present in about 25 percent of men with prostate cancer, according to studies noted by the National Cancer Institute. Only a small number of pancreatic cancers carry these mutations, according to the American Cancer Society.

BRCA mutations often interfere with DNA repair, forcing cancer cells to rely on PARP to maintain their DNA and stay alive. As a result, PARP inhibitors are typically used on patients with BRCA mutations or other mutations that interfere with DNA repair pathways. For tumors that already have a hard time repairing DNA to keep the cancer cells alive, PARP inhibitors make it more difficult.

Types of PARP inhibitors and why they may be used

The three main types of PARP inhibitors for ovarian cancer are:

  • Lynparza® (olaparib)
  • Rubraca® (rucaparib)
  • Zejula™ (niraparib)

For prostate cancer, the U.S. Food and Drug Administration has approved two poly (ADP-ribose) polymerase (PARP) inhibitors for men with metastatic castration-resistant prostate cancer (mCRPC) who have certain genetic mutations, marking the first approvals of this newer drug class in prostate cancer:

  • Rubraca®  (rucaparib)
  • Lynparza (olaparib)

While these drugs may sometimes be used under different circumstances, they’re more often a part of treatment for patients with ovarian cancer who fall into one of the following categories:

  • They have a mutation in the BRCA gene or high amounts of other gene mutations
  • They have advanced or recurrent ovarian cancer
  •  They have responded well to a chemotherapy regimen with the drugs carboplatin or cisplatin ("platinum-based")

Sometimes, PARP inhibitors are used as maintenance therapy. Maintenance therapy for ovarian cancer refers to the use of PARP inhibitors after a chemotherapy regimen has successfully led to significant tumor shrinkage. Some women benefit from PARP inhibitors after chemotherapy even when the treatment seems to eradicate the cancer.

Ovarian cancer often returns after treatment has concluded—more than 80 percent of women with ovarian cancer experience a recurrence, according to the National Cancer Institute (NCI). Maintenance therapy aims to lower the risk of recurrence by eradicating undetectable traces of cancer that the chemotherapy missed.

When used as a maintenance therapy, PARP inhibitors may be combined with a drug called Avastin® (bevacizumab), a targeted therapy that helps treat cancer or slow its growth by preventing tumors from forming new blood vessels.

For ovarian cancer:

  • Olaparib may be used:
    • For advanced ovarian cancer that responded well to chemotherapy (meaning chemotherapy reduced the tumor’s size), in women with a BRCA mutation
    • For advanced ovarian cancer that has already been treated with two or three chemotherapy drugs, in women with a BRCA mutation
    • As a maintenance therapy alongside another drug (bevacizumab), if prior treatment with chemotherapy resulted in substantial tumor shrinkage, in women with a BRCA mutation (or other mutations)
    • For recurrent ovarian cancer that responded well to chemotherapy, in women with or without a BRCA mutation
  • Rucaparib may be used:
    • For advanced ovarian cancer that has already been treated with two or three chemotherapy drugs, in women with a BRCA mutation
    • For recurrent ovarian cancer that responded well to chemotherapy, in women with or without a BRCA mutation
  • Niraparib may be used:
    • As a maintenance treatment for ovarian cancer that responded well to chemotherapy, in women with or without a BRCA mutation
    • For advanced ovarian cancer that has previously been treated with several chemotherapy drugs, in women with a BRCA mutation
    • For women with non-BRCA mutations and recurrent, advanced ovarian cancer that has come back more than six months after a previous chemotherapy regimen consisting of several drugs

For pancreatic cancer, olaparib can be used if the cancer is advanced, has responded well to chemotherapy drugs, and doctors suspect or know that it carries a BRCA gene mutation. Olaparib has been approved to treat adult patients with metastatic prostate cancer who  had inherited gene mutations in the BRCA1 and BRCA2 genes and whose disease has not progressed after at least 16 weeks of first-line chemotherapy. In this case, olaparib may help prevent tumor growth or reduce the tumor’s size, but its effect on lengthening survival remains unclear.

How to prepare and what to expect

PARP inhibitors are most beneficial for cancers with specific gene mutations, such as BRCA mutations. Doctors can determine whether you carry these mutations by performing tests on a small piece of the cancerous tumor and a sample of blood or saliva. The procedure to remove a tumor sample and analyze it in a laboratory, called a biopsy, is a necessary part of the diagnostic process for most cancers, including ovarian, prostate and pancreatic cancer.

Many patients will have their tumor sample genetically tested at the time of diagnosis. However, if you haven’t already undergone genetic testing, you will usually need to do so before starting treatment with a PARP inhibitor.

  • PARP inhibitors come in pills or tablets and are taken by mouth.
  • Depending on the type of PARP inhibitor, you may need to take the medication once or twice daily.
  • You should take the medicine at the same time or times each day.
  • It isn’t necessary to eat food before a dose.
  • If you’re directed to follow a twice-daily pattern, you should take the doses about 12 hours apart.

Before starting treatment with a PARP inhibitor, make sure that your doctor is aware of any prescription medications, over-the-counter drugs, vitamins or herbal medicines you’re taking. Your doctor will also need to know about any allergies you may have or problems with your liver, lungs or kidneys. PARP inhibitors shouldn’t be used if you’re pregnant, breastfeeding or planning to become pregnant.

Risks

Like most drugs, PARP inhibitors may cause side effects. Some of the more common side effects include:

  • Stomach upset (nausea, vomiting, diarrhea)
  • Tiredness
  • Poor appetite
  • Changes in sense of taste
  • Anemia (low red blood cells)
  • Abdominal pain
  • Joint and muscle pain

If you experience these or other side effects while taking a PARP inhibitor, be sure to report them to your doctor. Many of these side effects can be managed. For example, patients who experience nausea may be given anti-nausea medication. If this intervention doesn’t help and nausea persists, your doctor may recommend lowering the PARP inhibitor’s dosage.

In rare cases, PARP inhibitors have been linked to certain blood cancers, including myelodysplastic syndrome and acute myeloid leukemia, according to the American Cancer Society. For this reason, doctors regularly measure the number of white and red blood cells in your blood. If white or red blood cell counts are severely low for more than a couple of days, you may be advised to discontinue treatment with PARP inhibitors. You may be able to resume the drug at a lower dose if the issue goes away. However, if low blood cell counts persist, it may be a sign of blood cancer.

Benefits and results

PARP inhibitors can be beneficial when used in appropriate circumstances. According to the NCI and other more recent research on these agents, alone and in combination, it seems that PARP inhibitors may help reduce the size of certain tumors and limit their ability to grow. However, more research is needed to establish how much they can extend a patient’s life.

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