The Promise of PARP Inhibitors for Ovarian Cancer Treatment

While PARP inhibitors are available to almost all patients, women with BRCA gene mutations or whose tumors have HRD may benefit the most from these drugs. The label homologous recombination deficient (HRD) indicates a tumor which has one of many possible errors in the double stranded DNA repair process of homologous recombination.

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 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.

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.

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."

What Are The Side Effects?

"PARP inhibitors are taken orally as a pill, rather than an injection, which is nice for patients," Dr. Sonnenburg says. They work at the genetic level, preventing cancer cells damaged during chemotherapy from repairing themselves, and spreading.

Typically, there's a little bit of nausea for the first few weeks you're on the medication, but for most people it resolves as their body adjusts.

"If the nausea becomes severe, it can usually be treated with anti-nausea medications such as Zofran or Compazine. I’ve had some success with patients who take Zofran before taking their PARP inhibitor pill each day, and they’ve noticed an improvement. I’ve also had other patients take a low dose of Ativan, which has seemed to improve their nausea,” Dr. Sonnenburg says.

PARP inhibitors can lower red blood cell and platelet counts, which may lead to anemia and bring on fatigue. Sometimes the drug dosage can be adjusted, "but patients can also work through this, not by us fixing the anemia, but by increasing their exercise. I’ve seen patients who begin an exercise regimen, or increase their walking or jogging, and their symptoms have improved."

They have less fatigue, and are better able to tolerate their medication after boosting their activity level.

Some patients experience stomach upsets with PARP inhibitors. But symptoms are fairly mild, and they tend to subside over time. "Over-the- counter treatments such as Imodium or Pepto-Bismol are effective in some circumstances, and they can certainly help with stomach upset or diarrhea."

Overall, patients feel well on PARP inhibitors, and they’re able to live a normal life, says Sonnenburg. It's not like being on chemotherapy actually it's a nice relief for a lot of patients who’ve finished their chemo with CarboTaxol to switch over to maintenance PARP inhibitors. Most adjust quickly and don't experience a lot of long-term side effects.

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