PARP Inhibitors for Ovarian Cancer Treatment: Weighing Risks and Benefits

Most oncologists agree that this is a promising time for ovarian cancer therapies, especially with expanded FDA approval for a class of drugs known as PARP inhibitors. PARP inhibitors work by preventing cancer cells from repairing their damaged DNA, so the cells die off rather than spreading. PARP inhibitors have been shown to be most effective in women who carry a BRCA-1 or BRCA-2 gene mutation, though they are now approved and used for a wider group of ovarian cancer patients and at more stages of treatment regardless of genetic make up.

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.

There are 3 PARP inhibitors currently approved to treat ovarian cancer: Lynparza (olaparib), Zejula (niraparib), and Rubraca (rucaparib). And doctors anticipate there may be more approvals on the horizon. The drugs are used in combination with a patient’s individual plan for surgery, chemotherapy, radiation, and immunology. Your doctor may try different dosages and different types to find the most effective one for you.

PARP Side Effects

“PARP inhibitors I believe overall are safe, but as with any medication they have potential toxicities or side effects,” says Dr. Lynn Parker, gynecologic oncologist at Norton Cancer Institute.

There are three class-related side effects, meaning they’re common to all three PARPs:

• Fatigue is one of the most common side effects that patients experience
• Gastrointestinal, or GI side effects, are also common. These can include nausea, constipation or diarrhea, perhaps indigestion. The severity of the side effects vary: some patients may experience little to none of the GI side effects while others may have more pronounced symptoms
• The drug also affects the bone marrow, which in turn affects white blood cells, red blood cells, and platelet counts

In addition to these “buckets” of side effects, each PARP comes with its own potential toxicities, which is why your medical history will inform your doctor’s decision about using them. For instance, a woman with a history of drinking or compromised kidney function, for example, may be a less optimal candidate since one drug’s side effects may include the risk of impaired liver and kidney function.

“As a patient, being aware of what’s possible is important,” says Dr. Parker. But “patients and doctors have to work as a team, communicate well and often, so that if you do develop a side effect we are aware and can intervene on your behalf.”

The Catch?

The catch is that PARP inhibitors can be costly and insurance co-pays can vary substantially. Some insurance plans limit drug approvals to certain cases, and some don’t cover them at all. “PARP inhibitors are expensive, but there are ways to access these medications,” Dr. Parker says. “There are resources available for patients. Typically, we are able to get the drugs for the majority of our patients either through support from the drug companies that make them, or through charity funds in our hospital system, or other resources that are out there for patients.”

There may be other options for patients to receive financial assistance. Your gynecologic oncologist’s office may be able to help you find them.

Who Should Use PARP Inhibitors?

Weighing the risks and benefits of PARP inhibitors is a balancing act that is determined by doctors and patients together. Even patients who don’t have a BRCA mutation will see a benefit of many months, many doctors say. Others add that the side effects, while severe, are relatively mild when compared with other kinds of chemotherapy.

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.

For newly-diagnosed patients, Zejula has been approved by the FDA for all women with newly-diagnosed ovarian cancer regardless of HRD or BRCA status. The drug is used after successful treatment with a platinum-based chemotherapy, the mainstay chemotherapy for ovarian cancer.

Lynparza 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.

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).

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 (homologous recombination deficiency). 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 toxicities 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 who 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.”

The bottom line when it comes to adding a PARP inhibitor to your medical plan is to talk openly to your doctor about whether the treatment stands a good chance of being effective for you, and worth the side effects, potential risk, and cost.

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