Which Ovarian Cancer Patients Do Best on 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, and then in what’s called maintenance therapy, newer research has shown that almost all women can consider using PARP inhibitors throughout their treatment.

PARP inhibitors work by preventing cancer cells damaged by chemotherapy from repairing themselves and spreading. They've been shown to be most effective in patients who have a BRCA-1 or BRCA-2 mutation, says Dr. Dan Sonnenburg, medical oncologist at Community North Cancer Center. And we're now finding out that patients with what's called homologous repair deficiency are having great success as well.

Homologous Recombination Deficiency refers to the inability of cancer cells to repair themselves properly, which can make them a little easier to fight.

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.

There's a lot that goes into the decision making process about whether to prescribe PARP inhibitors. Some of it is based on how a patient is doing at that point in time. Doctors want their patients to have improved from their chemotherapy back to their baseline, and be back to their daily routine. They’ll want to make sure that most of the side effects from their chemotherapy have resolved anemia in particular. Because PARP inhibitors can certainly lower a patient’s red blood cell count. They want to make sure they’re starting you from a good place.

The Food and Drug Administration has approved Zejula (niraparib) 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. The PARP inhibitor Lynparza (olaparib) is 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.

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."

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