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The addition of olaparib (Lynparza) to standard treatment significantly improved disease-free survival (DFS) in patients with early, high-risk HER2-negative breast cancer and germline BRCA mutations, according to results from a phase III study.

Interim findings from the OlympiA trial showed that patients receiving the PARP inhibitor had a 42% reduction in the risk of invasive DFS versus patients receiving placebo (HR 0.58, 95% CI 0.41-0.82), and a 43% reduction in the risk of distant DFS (HR 0.57, 95% CI 0.39-0.83), reported Andrew Tutt, MB, ChB, PhD, of the Institute of Cancer Research and Kings College in London.

"The OlympiA study is the first study to report the benefits of a PARP inhibitor, olaparib, as an adjuvant treatment for early forms of germline BRCA-associated cancer," said Tutt during a press briefing held in advance of the American Society of Clinical Oncology (ASCO) virtual meeting. "These results suggest olaparib for 1 year after standard of care treatments provides meaningful benefit to germline BRCA-mutation carriers with high recurrence risk and HER2-negative breast cancer."

Reductions in DFS were "highly statistically significant, as it needed to be to meet the stringent criteria for an interim analysis," said Tutt.

Findings from the study were published simultaneously in the .

While outcomes are generally good for most patients with early breast cancer and germline BRCA1/2 mutations who received standard treatments, the risk of recurrence remains high for some. "So, additional or adjuvant novel targeted treatments are needed," said Tutt.

"These results are very important, since 5% of all breast cancers are associated with the BRCA1/2 mutations, and some of these cancers are aggressive," commented ASCO President Lori J. Pierce, MD. She noted that, in addition to demonstrating the reductions in invasive recurrence and distant disease with olaparib, the study "further highlights the significance of genetic testing in appropriate patients so that we know which patients will benefit from this therapy."

"I think it may even open the doors to additional trials for adjuvant PARP inhibitors for other BRCA1/2-associated cancers," Pierce added.

While olaparib is already approved in the metastatic setting in germline BRCA mutation carriers, OlympiA included germline BRCA mutation carriers with HER2-negative early breast cancer. The randomized, double-blind study enrolled 1,836 patients who had already received standard adjuvant or neoadjuvant chemotherapy, surgery, and radiation therapy.

Patients were randomized to receive either olaparib or placebo for 1 year, with a primary endpoint of invasive DFS (a combination of local recurrence of breast cancer, metastatic recurrence of breast cancer, other new cancers, and death due to any cause). Secondary endpoints included overall survival, and distant DFS (a combination of metastatic breast cancer, new cancer, and death due to any cause).

At a median of 2.5 years follow-up, patients who received standard treatment plus olaparib had an estimated 3-year invasive DFS of 85.9% versus 77.1% for patients who received standard treatment plus placebo. Distant DFS also improved with olaparib (87.5% vs 80.4% with placebo).

The 3-year estimated overall survival was also greater with olaparib compared with placebo (92.0% vs 88.3%), but the difference was not statistically significant, which Tutt explained was inevitable considering the early follow-up.

Adverse events (AEs) with olaparib were consistent with those already shown in previous studies and in approved labels, Tutt reported. Significant AEs (grade ≥3) more common with olaparib included anemia, lower levels of white blood cells, and fatigue. Olaparib did not increase serious AEs such as hospital admissions or the occurrence of leukemia or other cancers, said Tutt.