IDMC Concluded Lynparza Trial Crossed Superiority Boundary for Invasive Disease-Free Survival

The OlympiA Phase III trial for AstraZeneca and MSD’s Lynparza will move to early primary analysis and reporting following a recommendation from the Independent Data Monitoring Committee (IDMC).

Based on the planned interim analysis, the IDMC concluded that the trial crossed the superiority boundary for its primary endpoint of invasive disease-free survival (iDFS) and demonstrated a sustainable, clinically relevant treatment effect for Lynparza versus placebo for patients with germline BRCA-mutated (gBRCAm) high-risk human epidermal growth factor receptor 2 (HER2)-negative early breast cancer, and recommend primary analysis now take place.

The OlympiA Phase III trial is a partnership between Breast International Group (BIG), NRG Oncology, the US National Cancer Institute (NCI), Frontier Science & Technology Research Foundation (FSTRF), AstraZeneca and MSD. The trial is sponsored by NRG Oncology in the US and by AstraZeneca outside the US.

An estimated 2.3 million women were diagnosed with breast cancer worldwide in 2020, and BRCA mutations are found in approximately 5% of breast cancer patients. Around 55-65% of women with a BRCA1 mutation and approximately 45% with a BRCA2 mutation will develop breast cancer before the age of 70.

“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. 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,” Andrew Tutt, Global Chair of the OlympiA Phase III trial and Professor, Institute of Cancer Research and Kings College London, said.

“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, Oncology R&D, said.

“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 and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said.

In its communication, the IDMC did not raise any new safety concerns. The trial will continue to assess the key secondary endpoints of overall survival and distant disease-free survival.

Breast cancer is the most common cancer among women worldwide and an estimated 90% of all breast cancer is diagnosed at an early stage. Breast cancer is one of the most biologically diverse tumor types with various factors fueling its development and progression. The discovery of biomarkers in the development of breast cancer has greatly impacted scientific understanding of the disease.

BRCA1 and BRCA2 (breast cancer susceptibility genes 1/2) are human genes that produce proteins responsible for repairing damaged DNA and play an important role maintaining the genetic stability of cells. When either of these genes is mutated or altered such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly, and cells become unstable. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer and confer sensitivity to PARP inhibitors including Lynparza.