Ovarian Cancer

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PARP Inhibitors: Recent Approvals

Dr. Heidi Gray Seattle Cancer Care Alliance

Recent Niraparib Approval for Maintenance Therapy

  • Maintenance therapy using niraparib was recently approved by the FDA for women regardless of genetic make-up
  • Maintenance therapy is intended to prolong the time that a patient is cancer free, or prevent or postpone cancer from worsening
  • The PRIMA study showed improved progression-free survival of five to six months in women using niraparib
  • Expanded use of PARP inhibitors means they may now be offered to almost all women with ovarian cancer

Ovarian cancer treatment is complex, and there are many strategies for attacking the disease. One of the newest treatments is a class of drugs called PARP inhibitors. These drugs stop rapidly-dividing cancer cells from repairing their own genetic damage, preventing them from replicating. Three of these drugs have recently been approved to treat ovarian cancer:

“It’s really an amazing breakthrough,” says Dr. Heidi Gray, gynecologic oncologist at the Seattle Cancer Care Alliance. “We had a nine-year dearth of new drugs available for ovarian cancer patients, which was awful. So it’s really an exciting time to be treating ovarian cancer and offering these therapies for patients, and giving them more hope.”

The Food and Drug Administration (FDA) has now approved the PARP inhibitor niraparib (ZEJULA) for maintenance treatment of women with ovarian cancer who are responsive to first-line platinum-based chemotherapy.  In a study called PRIMA, using niraparib showed an improved, progression-free survival advantage of five to six months. The niraparib approval is not limited to women with a BRCA mutation, in contrast to FDA approvals for other PARP inhibitors.  Niraparib is approved for all women after a response to chemotherapy, regardless of the presence of a BRCA mutation.

Most recently, the American Society of Clinical Oncology (ASCO) released new guidelines recommending PARP inhibitors be offered to women, with or without genetic mutations, who are newly diagnosed with stage III or IV ovarian cancer and have improved with chemotherapy.

The PARP Advantage
Treatment for ovarian cancer typically involves first-line treatment, usually a combination of surgery and chemotherapy. Since ovarian cancer cells can be stubborn, some doctors also recommend maintenance therapy to help prevent recurrence.

Recent studies suggest that using PARP inhibitors — either as first-line therapy, maintenance therapy, or both — significantly extends the length of time patients are cancer-free or their cancer worsens.

In patients with advanced cancer, who have a high chance of their cancer returning, PARP inhibitors may reduce the risk of recurrence. They are most effective for patients who have a BRCA1 or BRCA2 gene mutation, and for those who have fast-growing, high-grade disease. Recent studies suggest that niraparib in particular may be an appropriate therapy for all ovarian cancer patients, regardless of whether they carry a BRCA mutation.

Tailored Treatment
Not every ovarian cancer patient responds the same way to treatment with PARP inhibitors. Instead, how you respond to treatment depends on a variety of factors, including the extent of disease, your genetic or hereditary risk, and whether the tumor itself has a mutation that a PARP inhibitor can use as a target.

The two groups that seem to benefit the most:
1.  Women with a BRCA1 or BRCA2 mutation: “Patients who have BRCA mutations are more susceptible to not being able to repair the DNA in the cancer cells, so the PARP inhibitors act as a sort of one-two hit in their ability to kill off the cancer cells,” Dr. Gray says.
2.  Women whose tumors express something called a homologous recombination deficiency profile (HRD): With HRD, there’s a switch in DNA that allows the cancer cell to continue to divide. When you have a deficiency in the homologous recombination, that makes it so that the cancer cells can’t repair themselves and are more vulnerable to PARP inhibitors.

“Patients who have BRCA mutations, or who have HR deficient tumors, should be counseled to consider maintenance therapy with a PARP inhibitor,” Dr. Gray says. Interestingly, studies suggest that all ovarian cancer patients, regardless of genetics may benefit from treatment with a PARP inhibitor.

Common Side Effects of PARP Inhibitors
Unfortunately, like all cancer therapies, PARP inhibitors come with side effects. Whether or not you’ll experience significant side effects from PARP inhibitors depends on several factors, including which PARP inhibitor you’re taking, what dose you’re ingesting, and whether you’re using it alone or in combination with other therapies.
Still, the side effects of most PARP inhibitor protocols include:

  • Nausea
  • Vomiting
  • Stomach upset
  • Fatigue

These side effects can be intolerable for some patients, but in almost every case, doctors can offer options to alleviate or even eliminate them.

Since PARP inhibitors disrupt how cells repair damaged DNA, killing off tumor cells and healthy cells simultaneously, the bone marrow and blood cells may take a hit. As a result, a subset of patients encounter side effects of PARP inhibitor treatment related to bone marrow suppression such as reduced blood cell and platelet counts.

Your doctor, patient education, and counseling can help you make decisions about cancer treatment, including PARP inhibitors like niraparib. Learning more about the drugs can help you understand your individual risks and benefits, given your own genetic profile and the disease you’re dealing with.

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Dr. Heidi Gray is a gynecologic oncologist at the Seattle Cancer Care Alliance. Read More