Olaparib Prolongs Invasive Disease-Free Survival in BRCA-Mutant, HER2- Breast Cancer

Patients with BRCA-mutated high-risk HER2-negative early breast cancer demonstrated a superior invasive disease-free survival when compared with placebo in the phase 3 OlympiA trial.

Patients with BRCA-mutated high-risk HER2-negative early breast cancer demonstrated a superior invasive disease-free survival (iDFS) when compared with placebo in the phase 3 OlympiA trial (NCT02032823), according to a press release from AstraZeneca and Merck & Co., Inc.1

The randomized, double-blind, parallel-group, multicenter trial has been moved to early primary analysis and reporting by recommendation of the Independent Data Monitoring Committee (IDMC) because of data from a planned interim analysis. These data showed the study crossed the superiority boundary for the primary end point of iDFS and showed that olaparib has a sustainable and clinically relevant treatment effect versus placebo for the trial’s patient population.

“We are delighted that our global academic and industry partnership has been able to help investigate a possible personalized treatment for women with hereditary breast cancer,” Andrew Tutt, MD, PhD, global chair of the OlympiA phase 3 trial and professor at the Institute of Cancer Research and Kings College London, said in a statement. The OlympiA trial is a partnership between the Breast International Group, NRG Oncology, the US National Cancer Institute, Frontier Science & Technology Research Foundation, AstraZeneca, and Merck.

“The most common cause of hereditary breast cancer is an inherited mutation in the BRCA1 or BRCA2 genes which also may cause the disease to develop at a significantly earlier age than is usual,” Tutt continued. “The OlympiA trial has allowed us to go beyond using genetic testing to identify patients who are at risk of this disease and explore the potential of [olaparib] to prevent disease recurrence for these patients. We look forward to analyzing and presenting the full results of the trial at a forthcoming medical meeting.”

There were 1836 patients with HER2-negative or triple-negative breast cancer, germline BRCA1 or BRCA2 mutations, who have completed adequate breast and axilla surgery, as well as 6 or more cycles of neoadjuvant or adjuvant chemotherapy, with an ECOG performance status of 0 or 1 randomized 1:1 on this study. These patients either received olaparib orally twice a day at 300 mg or placebo orally twice a day.

Any patients who had previously received a PARP inhibitor, had second primary malignancy, concomitant use of CYP3A inhibitors, or evidence of metastatic breast cancer were excluded from the trial.

“Breast cancer remains one of the most common cancers globally and despite advances in treatment, many patients with high-risk disease will, unfortunately, develop a recurrence. We look forward to reviewing the results,” José Baselga, executive vice president of Oncology R&D, said in a press release.

Previously, olaparib was approved by the FDA for the treatment of adult patients with germline BRCA-mutated metastatic breast cancer based on the OlympiAD trial (NCT02000622).2 These patients had been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting before receiving olaparib.

For the OlympiA trial, the IDMC did not bring up any new safety concerns when recommending the study for early analysis. The investigators continue to assess the key secondary end points of overall survival and distant disease-free survival. Other end points include the incidence of new cancers, health-related quality of life, and safety and tolerability.

“Analysis of the OlympiA trial, based upon the IDMC recommendation, could represent a potential step forward for patients with early-stage, high-risk primary breast cancer with a germline BRCA mutation,” Roy Baynes, senior vice president, head of global clinical development, and chief medical officer of Merck, said in a statement.


1. IDMC has concluded that OlympiA trial of Lynparza (olaparib) crossed superiority boundary for invasive disease-free survival vs. placebo at planned interim analysis. News release. AstraZeneca and Merck & Co., Inc. February 17, 2021. Accessed February 18, 2021. https://bit.ly/37uivWK

2. FDA approves olaparib for germline BRCA-mutated metastatic breast cancer. FDA. January 12, 2018. Accessed February 19, 2021. https://bit.ly/37uWhnJ