Bay Area Expert Explains How PARP Inhibitors Provide Hope for Ovarian Cancer

Doctors are looking at a woman's specific tumor and figuring out a unique course of care. Specifically, they may look for a "homologous recombination deficiency," which can indicate if the patient is a good candidate for PARP inhibitor treatments.

It's a genetic factor, sometimes present in women who have mutations in the BRCA gene. HRD means that a woman's ovarian cancer cells have trouble repairing themselves. And this can make them somewhat easier to fight.

What is the Goal of a PARP Inhibitor?

The goal of these drugs is to maintain the progress made by your surgery and chemotherapy, or to stop a cancer from progressing.

“There are three PARP inhibitors that are currently FDA approved and on the market,” says Chen, “and they’re all very similar in how they work against cancer.”

They vary a little bit in terms of how often they are taken: Some are given twice a day, some once a day. They also have slightly different side effects.

“As far as how we select treatment, it really depends on a personalized conversation with our patients about the schedule, or about anything in your medical history that would make me think that one drug was better than the other for you. And of course the level of evidence.”

The side effects of PARP inhibitors can be severe but are generally tolerable and manageable. They do include fatigue, and the drugs can affect your white blood cell counts so you need to be monitored when you’re starting treatments.

While initially, women with a BRCA-1 or BRCA-2 genetic mutation had been shown to respond especially well to PARP inhibitors when given after recurrence, newer research has shown that women with the BRCA gene mutation (and indeed almost all women) can consider using PARP inhibitors throughout their treatment.

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.

Quick Guide to How PARP Inhibitors Are Used for Ovarian Cancer

Just to make things easier because the various approvals can be confusing for patients:

1. The PARP inhibitor Zejula (niraparib) has been approved by the FDA for all women with newly-diagnosed ovarian cancer irrespective of whether the tumor is HRD positive (see above). The drug is used after successful treatment with a platinum-based chemotherapy, the mainstay chemotherapy for ovarian cancer.
2. Due to limited benefit in progression free survival seen in the absence of HRD, gynecologic oncologists differ on whether PARP inhibitors should be universally recommended in the "upfront maintenance setting." Each patient should be made aware of risks and benefits to PARP inhibitor maintenance and decide with their oncologist what is the best treatment plan for them.
3. The PARP inhibitor Lynparza (olaparib) is approved for women newly diagnosed with ovarian cancer and with a germline or somatic mutation in BRCA1/2.
4. Lynparza is also approved in combination with Avastin (bevacizumab) for women with HRD.  Avastin is a blood vessel growth inhibitor, which works by starving the tumor of vital nutrients needed to grow.

Using PARPs to Treat Recurrence

Unfortunately, too often, ovarian cancer comes back.

For women with ovarian cancer who have had a recurrence and responded to platinum-based chemotherapy, Lynparza, Zejula and another PARP inhibitor called Rubraca (rucaparib) are FDA approved for use as a maintenance therapy, regardless of whether a woman has a BRCA mutation or HRD.

For some women who have had prior chemotherapy treatments, Rubraca, Zejula or Lynparza may also be options. These uses are based on factors such as number of prior therapies and BRCA mutation or HRD.

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