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)
• Rucaparib (brand name Rubraca)

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.

Who Can Receive PARP Inhibitors?

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) 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.

The PARP inhibitor Zejula (niraparib) has been approved by the FDA for all women with newly-diagnosed ovarian cancer irrespective of whether the tumor is HRD or the patient has BRCA. The drug is used after successful treatment with a platinum-based chemotherapy, the mainstay chemotherapy for ovarian cancer.

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.

Unfortunately, too often, ovarian cancer comes back.

For women with ovarian cancer who have had a recurrence and responded to platinum-based chemotherapy, Lynparza, Zejula and Rubraca are FDA approved for use as a maintenance therapy, regardless of whether a woman has a BRCA mutation or HRD.

For some women who have had prior chemotherapy treatments, Rubraca, Zejula or Lynparza may also be options. These uses are based on factors such as number of prior therapies and BRCA mutation or HRD.

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.

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