New PARP Inhibitor Approval
- Olaparib was recently approved by the FDA for use with bevacizumab (Avastin) as maintenance therapy for ovarian cancer
- Olaparib and bevacizumab had already been approved separately for maintenance
- The drugs are approved for treatment following response to platinum chemo
“With each subsequent trial, we are able to further tailor therapy for patients,” says Dr. Alpa Nick, a gynecologic oncologist at Tennessee Oncology in Nashville. “It’s also exciting for patients because it helps us to better tailor their therapy based on direct information — on either germline or tumor mutation status — rather than randomly picking therapy in an all-comer population.”
Two Types of Gene Mutations
Read More- 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.
A New Combination Drug Therapy
Clinical trials also test the effectiveness of approved drugs, when used together. Combination drug therapies are often more powerful than drugs used separately, but their combined use must also be tested to confirm their effectiveness and approved for such use by the FDA. For ovarian cancer treatment, two existing drugs — olaparib (brand name, LYNPARZA) and bevacizumab (brand name, Avastin) — have recently been found to offer benefits when used in combination, the recent PAOLA study showed. “The most recent olaparib approval is actually really interesting,” says Dr. Nick. “This was a really important clinical trial.”The reason, says Dr. Nick, is because olaparib was combined with bevacizumab — which, she says, is “one of the other drugs we’ve used for maintenance therapy in advanced ovarian cancer.”
Most recently, the American Society of Clinical Oncology (ASCO) released new guidelines recommending 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.
Study Findings
The study looked at patients who were being treated with platinum-based chemotherapy — the standard for ovarian cancer — plus bevacizumab. Some of them were randomly chosen to receive the combination drug therapy — adding olaparib to their existing bevacizumab therapy — while others received bevacizumab plus a placebo.
“So it looked at whether adding olaparib to bevacizumab maintenance therapy improved outcomes in patients with advanced ovarian cancer,” Dr. Nick explains. “And it did show that there was an improvement in progression-free survival,” among women who received the combination therapy of olaparib plus bevacizumab.”
“The positive results led to the initial FDA approval for this combination,” she says. “The difference in survival was approximately six months.”
Dr. Nick said she now has patients who have been on this drug combination.
Other Findings
The study also looked at a subset of patients who did not have BRCA mutations. Among those women, the study data showed benefits from the combined drug therapy, “but not as great a magnitude of benefit in women who did not have BRCA mutations,” says Dr. Nick.
The group that did not benefit from the drug combination were those whose tumors do not have homologous recombination deficiency (HRD). HRD means that a woman's ovarian cancer cells have trouble repairing themselves. And this can make them somewhat easier to defeat. In patients without HRD, adding olaparib to bevacizumab did not improve progression-free survival.
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."
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