PARP Inhibitors for Ovarian Cancer
- PARP inhibitors help prolong remission
- Niraparib is available for women for the treatment of ovarian cancer, regardless of BRCA mutation
- Response is much greater in women with BRCA mutations and positive HRD status (a molecular measure that predicts PARP effectiveness)
- Side effects with PARP inhibitors are common, but they can be managed
“One of the really exciting things about being in the field of ovarian cancer at this point in time is that we have a whole succession of exciting new FDA approvals for what’s called maintenance therapy after chemotherapy, after initial diagnosis of ovarian cancer,” says Dr. Lisa Diver, a gynecologist oncologist at Sutter Bay Research Foundation in the Bay Area. “So, after your debulking surgery and your six cycles of chemotherapy, your doctor may suggest taking another medication during remission as maintenance therapy.”
Read MoreThere are three different PARP inhibitors that are now FDA-approved for maintenance therapy in ovarian cancer:
“Depending on the details of the genetics of your tumor and your own personal case, your doctor might recommend one or the other,” says Dr. Diver. “Both have been shown to be effective at prolonging the time until the cancer comes back. Olaparib is approved for women who have BRCA mutations in their tumors. Niraparib is now approved for almost all women after initial therapy for ovarian cancer.”
The Case for Niraparib
While PARP inhibitors seem to be most effective for patients who have a BRCA-1 or -2 mutation, and those who have fast-growing, high-grade disease, recent studies suggest niraparib in particular may be an appropriate therapy for all ovarian cancer patients, regardless of whether they carry a BRCA mutation.
Recent trials show niraparib, in particular, is also effective for patients whose tumors express something called a homologous recombination deficiency profile (HRD). With homologous recombination, there’s a switch in DNA that allows the cancer cell to continue to divide. When you have a deficiency in the homologous recombination, that makes it so that the cancer cells have difficulty repairing themselves. In recent trials, a BRCA mutation or HRD deficiency will predict a much stronger response to niraparib.
“What’s really exciting is that all patients, regardless of the genetics of their tumor, have on average seen benefit,” Dr. Diver says. If your doctor prescribes a PARP inhibitor, you’ll take the medication by mouth at home every day, monitor side effects and check in with your doctor regularly to assess your blood counts and ensure the medication is safe for you.
PARP Inhibitor Side Effects
Unfortunately, like all cancer therapies, niraparib comes with side effects. Whether or not you’ll experience significant side effects depends on several factors, including what dose you’re ingesting, and whether you’re using it alone or in combination with other therapies.
Like all PARP inhibitors, the common side effects of niraparib include:
- Nausea
- Vomiting
- Stomach upset
- Fatigue
No matter which PARP inhibitor protocol you’ve embarked on, doctors can modify your treatment schedule to reduce side effects. A few possibilities:
- Discontinue treatment for a brief time period
- Reduce the dose
- Transition to another PARP inhibitor to see if there’s any improvement
As with all cancer-related treatment, it will be important to incorporate counseling about the risks and benefits of PARP inhibitor maintenance, and help patients understand their individual likelihood of benefit given their germline genetic and tumor characteristics.
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."
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