PARP Inhibitors: A ‘Game Changer’ in Ovarian Cancer Treatment

“PARP inhibitors have changed the way we practice medicine for women with ovarian cancer,” says Dr. Melissa Geller a gynecologic oncologist at University of Minnesota Health Cancer Care. They’ve been a game-changer in terms of prolonging disease progression.

Taken as a pill, PARP inhibitors target ovarian cancer at the genetic level, preventing cancer cells from repairing their own damaged DNA, causing them to die. Genetic testing is the first step to determine whether a woman is a good candidate for the drug.

“At the University of Minnesota, all of our patients with newly diagnosed ovarian cancer are seen by genetic counselors,” says Dr. Geller. “We now know that about 50 percent of women with ovarian cancer may have either the BRCA-1 or BRCA-2 mutation, or other gene mutations. This puts them at higher risk for developing ovarian cancer, and leads to something called homologous recombination deficiency” — the inability of cells to repair their own DNA properly.

That’s why women with the BRCA mutation respond best to PARP inhibitors: Tumor cells with BRCA mutations already have trouble repairing their DNA. The PARP inhibitors make it that much harder, so the cells are more apt to die.

Who Can Take PARP Inhibitors?

While initially, women with a BRCA-1 or BRCA-2 genetic mutation had been shown to respond especially well to PARP inhibitors 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.

The Food and Drug Administration has now approved niraparib (brand name ZEJULA) for almost all women regardless of whether they have the BRCA mutation, as part of an initial course of treatment, or what’s called front-line treatment. That’s major news for ovarian cancer treatment. The PARP inhibitor Lynparza (olaparib) is also approved for women newly diagnosed with ovarian cancer and with a germline or somatic mutation in BRCA1/2. 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.

The American Society of Clinical Oncology (ASCO) guidelines recommend 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.

However, Dr. Amanika Kumar of the Mayo Clinic who spoke to SurvivorNet, cautioned that women still need to speak with their doctor to evaluate the benefit of taking a PARP inhibitor to extend life, because there are very real side effects due to the toxicity of the drug.

“Patients with HRD (homologous recombination deficiency) have a far better response than those without and those with BRCA mutations even more so. It is on us as clinicians to help patients understand the risks and benefits of treatment. Patients that have no mutation or HRD may choose not to go on maintenance (in fact I recommend they don’t) because there is real toxicity to these meds.”

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.

What Are The Side Effects of PARP Inhibitors?

Deciding on the best course of treatment is something for patients and their providers to discuss. While PARP inhibitors are promising, they still bring with them a risk of side effects. The most common include:

• Nausea – To tackle this, doctors often give patients an anti-nausea medication to take home as well.
• Vomiting
• Fatigue
• Upset stomach – this includes possible diarrhea, constipation, and abdominal pain.
• Various bone marrow-related side effects. While PARP inhibitors are highly effective against tumor cells, they may damage healthy bone marrow and blood cells as well, leading to immune system problems, lightheadedness, bleeding, and bruising.

PARP inhibitors may occasionally cause heart palpitations.

Side effects typically start to subside after a few weeks, but can sometimes take up to two months to resolve. And while they’re not terribly dangerous, they do need to be monitored.

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