The FDA granted accelerated approval to the PARP inhibitor olaparib for patients with advanced ovarian cancer who carry hereditary BRCA mutations and have previously received three or more lines of therapy. Olaparib is the first drug for ovarian cancer that is directed against specific mutations.

The FDA's recent approval of olaparib (Lynparza; AstraZeneca) provides a new treatment for some women with advanced ovarian cancer and may bring personalized medicine for the disease one step closer.

On December 19, the FDA endorsed olaparib, a PARP inhibitor, for patients with ovarian cancer who carry germline BRCA mutations and who have had at least three lines of therapy. A diagnostic test developed by Myriad Genetics that detects BRCA mutations in blood samples also received approval.

To support its action, the FDA cited a single-arm trial in which the drug induced objective responses in 34% of 137 women with advanced ovarian cancers. The median duration of response was 7.9 months. Whether olaparib improves overall survival in these patients remains unclear.

About 20% of patients with ovarian cancer have the hereditary BRCA mutations that make them eligible for olaparib, notes Ursula Matulonis, MD, of Dana-Farber Cancer Institute in Boston, MA, although some of these women can be cured by platinum-based therapies such as carboplatin.

“Approval of olaparib is a very positive step. It really expands the options for women with germline BRCA mutations,” Matulonis says. Several of her patients meet the criteria for the drug, and she plans to prescribe it for them. Before olaparib's approval, these women had only two treatment choices: join a clinical trial or receive chemotherapy with agents such as doxorubicin and paclitaxel.

Trials have also evaluated olaparib in breast, pancreatic, and prostate cancers. “The safety profile of this drug is reasonable, and it is mostly well tolerated,” says Eileen O'Reilly, MD, of Memorial Sloan Kettering Cancer Center in New York, NY, who has participated in studies of olaparib in patients with pancreatic cancer. It can trigger side effects that include fatigue and nausea, and there's a small risk of myelodysplasia, the decreased production of blood cells, she says.

The FDA's decision marks olaparib's first approval in the United States; European regulators sanctioned its use for advanced ovarian cancer in December, too. The approval also breaks new ground in another way: Olaparib is the only treatment for ovarian cancer that targets a specific genomic defect, Matulonis notes. Personalized medicine is the norm for breast cancer, she says, but “this is a first step toward personalized medicine for ovarian cancer.”

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