Who Should Be Taking PARP Inhibitors for Ovarian Cancer?

Ovarian cancer treatment is complex and often includes a variety of therapeutic options. One class of drugs, called PARP inhibitors, is increasingly showing promise in the fight against ovarian cancer.

“We are still prescribing PARP inhibitors, even in the current COVID-19 pandemic, because they have significant benefit for patients either for treatment of recurrent GYN cancers or as a maintenance therapy after initial chemotherapy for patients with advanced GYN cancers,” says Dr. Lynn Parker, a gynecologic oncologist at the Norton Cancer Institute in Louisville Kentucky.  Another advantage to PARP inhibitors during the pandemic is that these drugs are administered as pills, meaning that patients can take them at home, rather than reporting to an infusion center for intravenous chemotherapy.

Who Benefits from PARP Inhibitors

Recent studies suggest that using PARP inhibitors significantly extends the length of time patients are cancer-free or their cancer worsens.

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.  “While PARP inhibitors have been the most effective for patients who have hereditary risk, such as a BRCA-1 or -2 mutation, we also know there’s benefit for patients who have mutations in the tumor itself,” Dr. Parker says. The label homologous recombination deficient (HRD) indicates a tumor which has one of many possible errors in the double stranded DNA repair process of homologous recombination.

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. The Food and Drug Administration 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.

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.

PARP Inhibitors as Maintenance Therapy

After initial chemotherapy, studies suggest PARP inhibitors make sense for almost every ovarian cancer patient as a strategy to help reduce the risk of recurrence. So there’s a lot of excitement about the use of these drugs as a maintenance therapy to stave off disease.

“In patients with advanced cancer, even after optimal tumor reduction through surgery and initial chemotherapy, there’s a 50 to 60 percent chance of cancer coming back at some point,” Dr. Parker says. “There’s excitement about PARP inhibitors because it appears that these drugs can reduce the risk of the cancer recurring again in the future.”

Common Side Effects of PARP Inhibitors

Unfortunately, like all cancer therapies, PARP inhibitors come with side effects. Whether or not you’ll experience significant side effects from PARP inhibitors depends on several factors, including which PARP inhibitor you’re taking, what dose you’re ingesting, and whether you’re using it alone or in combination with other therapies.

Most PARP inhibitor protocols come with a risk of these side effects:

• Nausea
• Vomiting
• Stomach upset
• Fatigue

These side effects can be intolerable for some patients, but in almost every case, doctors can offer options to alleviate or even eliminate them. “I’ve found that having the patient adjust when they take the medication can have an impact, especially for the PARPs with once-a day dosing,” Dr. Parker says.

Deciding on PARP Inhibitors

While most patients with ovarian cancer should have the option to try a PARP inhibitor, those who respond best tend to have high-grade disease.

“High-grade cancers grow and divide more rapidly,” Dr. Parker says. “These cancers tend to be more responsive not only to chemotherapy, but also to PARP inhibitors as a maintenance therapy.”

Patients who have low-grade disease, meaning the cancer is growing more slowly, may benefit from another category of drugs, such as enzyme inhibitors and hormonal treatments.

No matter which category you fall into, it’s important to talk to your doctor about all available treatment options so you can make an informed decision. Ovarian cancer treatment is complex, but doctors have more tools at their disposal than ever before.

When it comes to the benefits the PARP inhibitor olaparib being used in combination with Bevacizumab (brand name Avastin) can have, the group that did not benefit were those whose tumors do not have homologous recombination deficiency (HRD). HRD means that a woman’s ovarian cancer cells have trouble repairing themselves. And this can make them somewhat easier to defeat.  In patients without HRD, adding olaparib to bevacizumab did not improve progression-free survival.

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 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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