How PARP Inhibitors Work For Ovarian Cancer

“PARP inhibitors are a class of oral medications, so they’re pills basically,” says Dr. Kellie Schneider, a gynecologic oncologist at Novant Health in Charlotte, North Carolina. “They decrease PARP, [a protein] which helps repair a cancer cell when there is DNA strand break. It helps make it a single-strand break as opposed to a double-strand break. PARP helps a cancer cell repair itself, and PARP inhibitors ensure that these cancer cells will die as opposed to being able to repair themselves.”

Patients with BRCA mutations respond best to PARP Inhibitors. According to Dr. Schneider, this class of drug helps both patients with an active disease and when they’re trying to maintain a remission.

“Like other treatments, PARP inhibitors have their own unique class of side effects,” she notes. “But a lot of patients have seen amazing benefits with 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 approved Zejula (niraparib) for patients with advanced cancer regardless of whether they have the BRCA mutation, as part of an initial course of treatment, or what’s called front-line treatment. In 2020, 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 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. Homologous recombination deficient (HRD) indicates a tumor which has one of many possible errors in the double stranded DNA repair. 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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