Olaparib’s OlympiA Trial Crossed the Superiority Limit for Invasive Disease-Free Survival versus Placebo

In 2020, an estimated 2.3 million women will be diagnosed with breast cancer worldwide, with BRCA mutations discovered in approximately 5% of those diagnosed. Breast cancer will strike 55% to 65% of women with a BRCA1 mutation and 45% of women with a BRCA2 mutation before they are aged 70 years.¹

Following a recommendation from the independent data monitoring committee, the phase 3 OlympiA study for olaparib will progress to early primary analysis and reporting. This news means that olaparib is a step closer to personalized treatment for women with hereditary breast cancer with an inherited mutation in the BRCA1 or BRCA2 genes—which are the most prevalent cause of hereditary breast cancer and can also cause the illness to begin at a younger age.¹

The OlympiA trial has allowed clinicians to look beyond genetic testing to identify patients who are at risk for being diagnosed with breast cancer, and to look into the possibility of utilizing olaparib to prevent disease recurrence in these individuals. Breast cancer remains one of the most common diseases worldwide, and despite breakthroughs in treatment, many patients with high-risk disease may unfortunately experience a recurrence. Analysis of the OlympiA trial, based on the independent data monitoring committee recommendation, could represent a potential step forward for patients with early-stage, high-risk primary breast cancer with a germline BRCA mutation.¹

BRCA1 and BRCA2 are 2 genes that have been linked to breast cancer. BRCA1 and BRCA2 are human genes that create proteins that repair damaged DNA and play a key role in maintaining cell genetic stability. When one of these genes is mutated or altered to the point that its protein product is not produced or functions incorrectly, DNA damage may not be repaired effectively, causing cells to become unstable. As a result, cells are more prone to generate additional genetic changes that may lead to cancer and make them more susceptible to poly (ADP-ribose) polymerase (PARP) inhibitors such as olaparib.

Olaparib is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response in cells and tumors with a homologous recombination repair deficit, such as BRCA1 and/or BRCA2 mutations. Olaparib inhibits PARP, causing PARP to bind to DNA single-strand breaks, slowing replication forks, their collapse, and the creation of DNA double-strand breaks, as well as cancer cell death. Olaparib is being evaluated in a variety of PARP-dependent tumor types with DNA damage response pathway abnormalities and dependencies.

Reference

1. AstraZeneca. IDMC has concluded that OlympiA trial of Lynparza crossed superiority boundary for invasive disease-free survival vs. placebo at planned interim analysis. February 17, 2021. www.astrazeneca.com/media-centre/press-releases/2021/olympia-trial-of-lynparza-idmc-recommend-early-analysis.html. Accessed December 11, 2021.