Decision Making Around PARP Inhibitors, Now That These Drugs Are an Option For Many More Women With Ovarian Cancer

For a growing number of women battling ovarian cancer, the treatment options have now expanded to include a new class of drug called PARP inhibitors. These drugs work by targeting the DNA–the genetic material–of cancer cells, preventing the cells from repairing themselves.

These drugs can be given both in early and later phases of cancer treatment, on their own or in concert with other chemotherapy drugs. All three types of PARP inhibitor drugs are administered orally, and women can take the pills at home or in a care setting after discussion with their medical team and a review of the drugs’ risks and benefits.

PARP inhibitor side effects can be very challenging, and women taking the medication must be closely watched for signs of toxicity, while managing common reactions which can range from gastrointestinal discomfort to anemia. In the era of COVID-19, specialists tell SurvivorNet this monitoring is still possible.

Whether you should consider a PARP inhibitor will likely be determined by a number of factors: the specific genetic make-up of your cancer, your disease stage, whether your cancer had a positive response to a so-called platinum based chemotherapy and your ability to tolerate the drug’s side effects.  “PARP inhibitors have revolutionized our treatment of ovarian cancer,” says gynecologic oncologist Dr. Saketh Guntupalli, University of Colorado/Denver.

Even though PARP inhibitors are now approved for almost all ovarian cancer patients, their effect is far greater in patients who have BRCA genetic mutations and something called homologous recombination deficiency (HRD). 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.

However, 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.

How PARP Inhibitors Work

PARP inhibitors target a specific enzyme and compromise cancer cells’ ability to repair themselves and replicate.  Patients with ovarian cancer who stand to benefit the most from PARP inhibitors carry the BRCA mutation which is associated with ovarian cancer as well as breast cancer.  However while 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. Most recently, the Food and Drug Administration has 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.

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.”

Originally prescribed after a cancer has come back in women with BRCA mutations, PARP inhibitors can now be offered after initial surgery and chemotherapy, and continued for months, or even years, as long as the side effects are tolerated. The option to offer these drugs to women even after their first course of a different treatment increases the number of patients who can benefit. PARP inhibitors can also be used to help suppress recurrence of the disease, possibly extending life expectancy by four or five months. Again, the decision making process here will vary greatly among women, and will likely include the potential benefit the drugs can have (based again on genetics and molecular information unique to you).

PARP Inhibitors at Home

One advantage to taking PARP inhibitors is their convenience, a term not often associated with the fight against cancer.  “They’re pills, so patients don’t have to spend hours and hours in a chemotherapy infusion center,” Dr. Guntupalli explains. “You take them at home. Oftentimes, with telemedicine, we’re able to follow patients from afar, without them having to come in to the office. I keep patients on them as long as they can tolerate it.  Generally, at about two years, we would consider taking the patient off because it’s an expensive drug and they do have side effects.”

The ability to use state-of-the-art cancer treatment at home, rather than having to report to a hospital or medical office for intravenous chemotherapy, is especially beneficial during the COVID-19 pandemic as cancer patients seek to reduce their chances of being exposed to the new coronavirus.

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