Deciding on PARP Inhibitors for Ovarian Cancer

Ovarian cancer treatment is complex and often includes a variety of therapeutic options. One of the newer treatments on the block, PARP inhibitors, show promise in the fight against ovarian cancer, particularly among women who carry a BRCA genetic mutation.

“If I was personally going through a gynecologic malignancy in an advanced stage I truly would want to be offered a PARP inhibitor after chemotherapy,” says Dr. Lynn Parker, gynecologic oncologist at the Norton Cancer Institute.

The PARP Advantage

Treatment for ovarian cancer typically involves an initial treatment, which is usually a combination of surgery and chemotherapy. Since ovarian cancer cells can be stubborn, most women will also begin maintenance therapy to help prevent recurrence.

Recent studies suggest that using PARP inhibitors — either as first-line treatment, maintenance therapy, or both, significantly extends the length of time patients are cancer-free or their cancer worsens. The studies tested the three PARP inhibitors as therapy for women with high-grade epithelial cancers (the ovarian tumors that are considered most aggressive, since the cells are most abnormal and will grow and spread more rapidly). The three PARP inhibitors are:

• Niraparib (brand name Zejula)
• Olaparib (brand name Lynparza)
• Veliparib (not yet FDA approved for ovarian cancer treatment)

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.

While PARP inhibitors are available to almost all women, women with BRCA gene mutations or who are HRD proficient may benefit the most from these drugs. 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.

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.”

Tailored Treatment

Not every ovarian cancer patient responds the same way to treatment with PARP inhibitors. How a woman’s cancer responds to these drugs depends on a variety of factors, including the extent of disease, the genetic or hereditary risk, and whether the tumor itself has a mutation that a PARP inhibitor can use as a target. But while some women respond to the therapy better than others, “the majority of patients with stage III and stage IV gynecologic malignancy should be offered PARP inhibitors,” Dr. Parker says.

As with any cancer therapy, treatment should be tailored to the individual patient. A few key strategies:

• Consider your health. If you’re healthy and fit, you’re more likely to tolerate a higher dose of treatment. On the flip side, if a patient is frail, it’s best to start with a lower dose and titrate up.
• Start low. Just because you start treatment at one dose doesn’t mean you have to stay there. “With biologic therapies, our bodies have to adjust to the treatment,” Dr. Parker says.
• Allow your body time to adjust. Side effects of treatment may level off after a period of time. Dr. Parker cites patients who start out on therapy with severe side effects, such as nausea or dizziness, but once their body adjusts to treatment, the side effects dissipate.

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.

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