You May Be Eligible for a PARP Inhibitor — How to Decide?

A new category of drugs, known as PARP inhibitors, have been revolutionary in the treatment of ovarian cancer. These drugs target a protein within cells known as PARP (full name: Poly (ADP-ribose) polymerase). This protein repairs damaged DNA within cancer cells. By inhibiting PARP, the DNA-repair system is disabled and cancer cells die.

Beyond BRCA Gene Mutations

Until recently, PARP inhibitors were mostly given to women with BRCA gene mutations. These drugs are now available to women without BRCA mutations as part of the first course of treatment, after you’ve had chemotherapy and surgery. Though the benefit is considerably less for women without these molecular characteristics.

It’s estimated that 44 percent of women who inherit a harmful BRCA1 mutation will develop ovarian cancer. Among those who test positive for BRCA2, about 17 percent are predicted to develop the disease. By comparison, about 1.3 percent of women in the general population will develop ovarian cancer sometime during their lives.

For patients with BRCA mutations, PARP inhibitors have been a game-changing advance in ovarian cancer treatment.

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.

Expanded Use: Thanks To New Study

Now, the use of PARP inhibitors has expanded to include a wider range of patients. 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.

The landmark PRIMA study, which was published in November 2019, was the first to look at the use of PARP inhibitors in everyone who is starting ovarian cancer treatment — not just those with BRCA gene mutations or those who have had their cancer recur.

“The interesting difference in this trial was it included all comers,” says Dr. Alpa Nick, a gynecologic oncologist at Tennessee Oncology in Nashville.

Nirapirib: Positive Findings

One drug, niraparib — one of three PARP inhibitors being used to treat ovarian cancer — was studied and found to be beneficial  after therapy (surgery and chemotherapy) is completed in the upfront setting, and after patients have shown a complete or partial response to platinum-based chemotherapy, the standard chemotherapy used to treat ovarian cancer, in the recurrent setting.

“Prior to the study,” says Dr. Nick, “frontline maintenance [with a PARP inhibitor] was mainly reserved for patients who had BRCA mutations. But now, patients who have received platinum-based chemotherapy and who have had a complete or partial response, are eligible for frontline maintenance with niraparib therapy.”

The study showed an improvement in progression-free survival — meaning a cancer does not advance — of approximately five to six months in patients who got maintenance niraparib versus those who received a placebo.

“So all patients benefited from PARP inhibitor maintenance therapy,” Dr. Nick explained, adding “and all women are now eligible after primary treatment for advanced ovarian cancer.”

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.”

HRD means that a woman’s ovarian cancer cells have trouble repairing themselves. And this can make them somewhat easier to fight.

What’s Approved and for When?

The PARP inhibitor Zejula (niraparib) is approved by the FDA for all women with newly diagnosed ovarian cancer irrespective of whether the tumor is HRD. 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 another PARP inhibitor called Rubraca (rucaparib) 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.