Options For Ovarian Cancer Maintenance Therapy: PARP Inhibitors & Avastin

"The first thing that we do is we make sure that all patients have genetic testing," says Dr. Alpa Nick, a gynecological oncologist with Tennessee Oncology in Nashville. “This is best done at the time of diagnosis or during the initial phase of treatment,” she says, "because that helps us to determine which patients will benefit the most from using a PARP inhibitor during maintenance therapy."

What Can Our Genes Tell Us?

There are two types of mutations doctors look for when they review genetic test results: germline and somatic.

Germline testing looks for the presence of genetic mutations in the whole body. So whether it's a skin cell, a breast cell, or a colon cell that's being examined, they will all show the same mutation. These mutations are hereditary, passed from parent to child; so the test results not only inform women of their own cancer risks but also those of family members.

Somatic testing looks at specific gene mutations within the tumor itself. Oncologists call these "driver mutations" because they can help doctors and patients choose the best available treatment options.

Armed with genetic testing results, patients will be able to make an informed choice about drug therapies: "The biggest question is: How do you choose between bevacizumab (brand name, Avastin) or a PARP inhibitor for maintenance therapy?" says Dr. Nick. The drugs have very different ways of combatting cancer cells. PARP inhibitors prevent cancer cells from repairing their DNA, while Avastin blocks the formation of new blood vessels, starving tumors of nutrients.

Early Decisions For Later Treatment

Your doctor will reference your genetic test results to help determine the best approach.

Women with a BRCA-1 or BRCA-2 genetic mutation had been shown to respond especially well to PARP inhibitors after recurrence, however 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. It’s important to make the decision about starting PARP inhibitors for maintenance as early as possible, since “the magnitude of benefit seems to be the greatest when they’re used earlier in the disease course."

In clinical trials, one of the three PARP inhibitors, olaparbib has been found to have a particular benefit for maintenance therapy when paired with bevacizumab (brand name AVASTIN).  The FDA approved bevacizumab to be used in conjunction with olaparib (brand name LYNPARZA) in HRD (Homologous Recombination Deficiency) positive women who show a response to platinum-based chemotherapy. The results of the trial showed an increase in progression-free survival from an average of 17 months to 37 months.

"So a patient really has to make a decision up front, or near the beginning of their treatment, that they want bevacizumab maintenance treatment because they'll have it with their primary chemotherapy," explains Dr. Nick. The drug is administered intravenously and can be given in combination with other chemotherapy drugs. Avastin works by affecting the growth of blood vessels, starving tumors of the blood they need as nourishment.

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.

Surgery offers another important decision point. "When patients have their surgery, we can test their tumor to decide if their tumor has a homologous recombination deficiency," known as HRD. If it does, that also suggests they would benefit from PARP inhibitor maintenance therapy," says Dr. Nick.

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 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."

No BRCA? No HRD? What Now?

What about patients who do not have a BRCA mutation and whose tumor doesn’t show an HRD? They still may have other genetic characteristics that place them at higher risk and will identify them as better candidates for bevacizumab.

And in some cases, tumor testing may show that both bevacizumab and a PARP inhibitor will be most effective when combined.

"I talk to these patients about giving bevacizumab with their postoperative therapy. Then, based on the newer data and their tumor testing we can add a PARP inhibitor to their maintenance therapy," says Dr. Nick.

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