Ovarian Cancer: Who Benefits From PARP Inhibitors?

Among women with ovarian cancer, “patients who have BRCA mutations,” are most likely to benefit from their use, she says. Dr. Wethington cites a large study where patients were randomly chosen to receive a PARP inhibitor after their primary therapy for ovarian cancer. “The vast majority of the patients had germline or inherited risk. And that study showed this unbelievable, tremendous benefit to patients receiving a PARP inhibitor.”

While initially, 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.

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 olaparib (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 homologous recombination deficient (HRD) tumors. These are tumors which have one of many possible errors in the double stranded DNA repair process.  Avastin is a blood vessel growth inhibitor, which works by starving the tumor of vital nutrients needed to grow.

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."

Genetic Testing For Ovarian Cancer

All women diagnosed with ovarian cancer should have genetic testing, if they haven’t done it already. A genetic test can provide valuable information for them and their family members, and also help to guide treatment decisions that target their specific cancer. Germline genetic testing looks for genetic mutations throughout the body. Somatic testing looks for mutations within the tumor. Both tests can provide valuable information to help guide treatment.

Post-Chemotherapy Recurrences

After successful initial treatment of ovarian cancer, a recurrence is unfortunately still possible, but doctors are prepared to treat it. If a patient’s cancer recurs six months or more after platinum-based chemotherapy — a standard amount of chemo treatment for ovarian cancer — the cancer is dubbed “platinum-sensitive.” If a cancer recurs within six months of the last platinum-based treatment, the tumors will be defined as “platinum-resistant.”

“If they have a platinum-sensitive recurrence,” Dr. Wethington explains, “they get chemotherapy treatment. Then they use the PARP inhibitor as maintenance, at that point. So those patients have shown a benefit in the platinum-resistance setting.”

What's Next For PARP Inhibitors?

The next frontier for PARP inhibitors may include combination therapy:  “Certainly the next question is whether to use PARP inhibitors in combination with other drugs,” says Dr. Wethington.

Researchers are especially interested in exploring combination therapies for patients who have recurrent ovarian cancer — what she calls “a real pesky tumor that keeps coming back”– even after multiple chemotherapy cycles.

“By then, most people have already gotten PARP inhibitors,” she explains, which can create a resistance response. “That’s why people are looking to see if there are combinations that could overcome the PARP resistance — to mix it up a little bit to make it more effective.”

Future PARP Inhibitor Combinations

The use of PARP inhibitors may also change over time, Dr. Wethington notes, “as we learn more about whether — and when — to use them with things like Avastin, or other targeted therapies, or maybe with immunotherapy.”

The new PARP inhibitors are considered revolutionary. Still quite new, they’re being studied by doctors trying to answer many questions about how best to use these drugs.

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