Monotherapy Improves Outcomes in Metastatic Breast Cancer With BRCA Mutation

An immuno-agent improves progression-free survival (PFS) and lowers the risk of death for patients with human epidermal growth factor 2 (HER2)-negative metastatic breast cancer and a germline BRCA mutation, according to a recent study published in the New England Journal of Medicine (online August 10, 2017; doi:10.1056/NEJMoa1706450).


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Olaparib has also shown promise as an anti-cancer therapy in patients with metastatic breast cancer and a germline BRCA mutation. However, research has yet to compare the effects of olaparib and standard therapy among patients with such disease.

Mark Robson, MD, Memorial Sloan Kettering Cancer Center (New York, NY), and colleagues conducted a phase III trial to compare the efficacy and safety of olaparib with that of standard therapy with single-agent chemotherapy of the physician’s choice among patients with HER2-negative metastatic breast cancer and a germline BRCA mutation. A total of 302 patients who had received no more than two previous chemotherapy regimens were randomly assigned (2:1) to receive olaparib tablets (300 mg twice daily, n = 205 patients) or standard therapy (capecitabine, eribulin, or vinorelbine in 21-day cycles; n = 97 patients).

The primary endpoint of the study was PFS, which was measured and assessed by blinded independent central review and analyzed on an intention-to-treat basis.

Results of the study showed that median PFS was significantly longer in the olaparib cohort (7.0 months) compared with the standard-therapy cohort (4.2 months.

Response rate also favored the olaparib cohort, with patients demonstrating 59.9% response compared with 28.8% in the standard-therapy cohort.

Additionally, olaparib proved to be a safer treatment option than physician-chosen chemotherapy. The rate of grade 3 or higher adverse events was 36.6% in the olaparib cohort, compared with 50.5% in the standard-therapy cohort. Likewise, the rate of treatment discontinuation due to toxic effects was 4.9% and 7.7%, respectively.

Authors of the study concluded that olaparib provides a more safe and effective treatment option than standard chemotherapy for patients with HER2-negative metastatic breast cancer and a germline BRCA mutation.

“Larger studies that investigate the differential treatment effects of olaparib among subgroups, particularly those defined according to hormone-receptor status or previous use of platinum-based therapy, would be helpful, as would a head-to-head study to determine the relative efficacy of olaparib and platinum-based chemotherapy,” they wrote.—Zachary Bessette