Phase 3 OlympiA Trial for HER2-Negative Breast Cancer Moves to Early Primary Analysis Per IDMC Recommendation

In the OlympiA trial, patients with high-risk HER2-negative breast cancer were randomized 1:1 to receive either olaparib or placebo for 12 months.

A planned interim analysis found that the phase 3 OlympiA trial (NCT02032823) crossed the superiority boundary for its primary end point of invasive disease-free survival (iDFS) and demonstrated a sustainable, clinically relevant treatment effect for olaparib (Lynparza) versus placebo in patients with germline BRCA-mutated (gBRCAm) high-risk HER2-negative early breast cancer, according to the agent’s co-developers, AstraZeneca and Merck.1

Based on this finding, the independent data monitoring committee (IDMC) has recommended the trial move to early primary analysis and reporting.

Notably, the IDMC did not raise any new safety concerns in its communication. Moving forward, the trial will continue to assess the key secondary end points of overall survival and distant disease-free survival.

“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. 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,” Andrew Tutt, PhD, global chair of the OlympiA trial and professor at the Institute of Cancer Research and Kings College London, said in a press release. “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 Lynparza 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.”

In this double-blind, parallel group, placebo-controlled, multicenter trial, patients with high-risk HER2-negative breast cancer were randomized 1:1 to receive either olaparib or placebo for 12 months.2 Patient enrollment began in April 2014 and the target number for randomization was 1500 patients across approximately 500 sites and approximately 25 countries worldwide.

Patients who were eligible for the trial must have completed local treatment and at least 6 cycles of neoadjuvant therapy composed of anthracyclines and/or taxanes. Stratification factors included hormone receptor status, prior neoadjuvant versus adjuvant chemotherapy, and whether patients had received platinum therapy for current breast cancer.

Olaparib is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells or tumors which harbor a deficiency in homologous recombination repair (HRR), such as mutations in BRCA1 and/or BRCA2. The agent is being tested in a range of PARP-dependent tumor types with defects and dependencies in the DDR pathway.

Currently, olaparib is approved in a number of countries for various indications in ovarian, breast, pancreatic, and prostate cancer and regulatory reviews are also underway in several countries for its use in these diseases.


1. IDMC has concluded that OlympiA trial of Lynparza crossed superiority boundary for invasive disease-free survival vs. placebo at planned interim analysis. News release. AstraZeneca. Published February 17, 2021. Accessed February 17, 2021.

2. Tutt A, Kaufman B, Garber J, et al. OlympiA: A randomized phase III trial of olaparib as adjuvant therapy in patients with high-risk HER2-negative breast cancer (BC) and a germline BRCA1/2 mutation (gBRCAm). Ann Oncol. 2017;28(suppl 5):v43-v67. doi: 10.1093/annonc/mdx362