The FDA has approved olaparib, a PARP inhibitor, for use in patients with metastatic breast cancer who also carry a germline BRCA1 or BRCA2 mutation. With the January 12 approval, olaparib becomes the first targeted therapy for patients with breast cancer with mutated BRCA.

The FDA has approved the oral drug olaparib (Lynparza; AstraZeneca) for patients with metastatic breast cancer who also bear germline BRCA1 or BRCA2 mutations. The January 12 approval marks the first targeted therapy approved for this indication as well as the first PARP inhibitor approved for breast cancer.

Olaparib was initially approved in late 2014 for BRCA-mutated advanced ovarian cancer, the first PARP inhibitor approved for any cancer. Expanding its indication to another population of patients is “a plus for science,” says Lori J. Goldstein, MD, director of The Naomi and Phil Lippincott Breast Evaluation Center at Fox Chase Cancer Center in Philadelphia, PA. “It's a plus for patients, especially for triple-negative BRCA-mutated cancer patients, for whom there is no previous targeted therapy approved.”


Structure of BRCA1

The drug's approval was based on the phase III OlympiAD trial, which enrolled 302 patients with HER2-negative, metastatic breast cancer and germline BRCA mutations (N Engl J Med 2017;377:523–33). Patients were randomly assigned to receive olaparib or the physician's chemotherapy of choice in a 2:1 ratio. Median progression-free survival was significantly longer among those treated with olaparib compared with chemotherapy (7 months vs. 4.2 months, respectively). In addition, the response rate for the PARP inhibitor was more than double that for chemotherapy: 59.9% versus 28.8%, respectively.

Patients also tolerated olaparib better than chemotherapy and reported a higher quality of life, says Mark Robson, MD, of Memorial Sloan Kettering Cancer Center in New York, NY, and OlympiAD's lead investigator. Although previous studies found that olaparib could, in rare cases, lead to hematologic malignancies such as myelodysplastic syndrome, Robson says, that didn't occur in the OlympiAD trial.

However, the drug didn't show an overall survival (OS) benefit. Median OS was slightly more than 19 months in both groups.

Assessing OS was difficult in this trial partly “because we don't control what treatment people get after they progress on the study,” Robson says. In fact, patients in the chemotherapy group were more likely to be later treated with a PARP inhibitor or platinum-based chemotherapy than those in the olaparib group. That could partially explain the lack of difference in OS, Robson says.

Patients with breast cancer who have germline BRCA1 or BRCA2 mutations represent only about 5% of all breast cancer cases, and those with metastatic disease are an even more limited group. Despite the small numbers, Robson is hopeful that olaparib's approval lays the groundwork for further expanding its use. A clinical trial testing olaparib in patients with early-stage BRCA-mutated breast cancer is under way, Robson says, adding that olaparib could also prove to be effective even in those without inherited BRCA mutations but whose tumors have acquired a BRCA1 or BRCA2 deficiency. –Rachel Tompa

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