Results from the OlympiA Phase III trial showed AstraZeneca and MSD's Lynparza (olaparib) demonstrated a statistically significant and clinically meaningful improvement in invasive disease-free survival (iDFS) versus placebo in the adjuvant treatment of patients with germline BRCA-mutated (gBRCAm) high-risk human epidermal growth factor receptor 2 (HER2)-negative early breast cancer.
The results will be presented during the plenary session of the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting on 6 June 2021 (abstract LBA#1) and were published today in The New England Journal of Medicine.
An estimated 2.3 million people were diagnosed with breast cancer worldwide in 2020 and BRCA mutations are found in approximately 5% of breast cancer patients.1,2
Sue Friedman, Executive Director, Facing Our Risk of Cancer Empowered (FORCE) and member of the OlympiA trial steering committee, said: "While there have been great strides in the early treatment of breast cancer, the fear of cancer returning is still at the forefront of patients' minds. New targeted treatment approaches are needed in the adjuvant setting that can help keep cancer and that fear at bay."
Andrew Tutt, chair of the OlympiA trial steering committee and professor of Oncology at The Institute of Cancer Research, London and Kings College London, said: "We are thrilled that our global academic and industry partnership in OlympiA has been able to help identify a possible new treatment option for patients with early-stage breast cancer and who have inherited mutations in their BRCA1 or BRCA2 genes. Patients with early-stage breast cancer who have inherited BRCA mutations are typically diagnosed at a younger age compared to those without such a mutation. Olaparib has the potential to be used as a follow-on to all the standard initial breast cancer treatments to reduce the rate of life-threatening recurrence and cancer spread for many patients identified through genetic testing to have mutations in these genes."
Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: "This is the first time that any medicine targeting a BRCA mutation has demonstrated the potential to change the course of early-stage breast cancer and offer hope for a cure. By providing a treatment which significantly reduces the risk of breast cancer returning in these high-risk patients, we hope Lynparza will set a new benchmark demonstrating sustained clinical benefit. We are working with regulatory authorities to bring Lynparza to these patients as quickly as possible."
Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: "Results of the OlympiA trial represent a potential step forward for patients with high-risk early breast cancer. These new data support the importance of testing at diagnosis for BRCA1/2 mutations, which are actionable biomarkers that can help identify patients with early breast cancer who may be eligible for adjuvant treatment with Lynparza. Testing for BRCA mutations in addition to hormone receptor status and the expression of the HER2 protein will allow clinicians to better inform potential treatment plans for their patients."
In the overall trial population of patients who had completed local treatment and standard neoadjuvant or adjuvant chemotherapy, results showed Lynparza reduced the risk of invasive breast cancer recurrences, second cancers or death by 42% (based on a hazard ratio [HR] of 0.58; 99.5% confidence interval [CI] 0.41-0.82; pLynparza remained alive and free of invasive breast cancer and second cancers versus 77.1% on placebo.
Lynparza also demonstrated a statistically significant and clinically meaningful improvement in the key secondary endpoint of distant disease-free survival (DDFS) in the overall trial population. Lynparza reduced the risk of distant disease recurrence or death by 43% (based on an HR of 0.57; 99.5% CI 0.39-0.83; pLynparza, but the difference in overall survival (OS) did not reach statistical significance. The trial will continue to assess OS as a secondary endpoint.
In February 2021, the Independent Data Monitoring Committee recommended for the OlympiA trial to move to early primary analysis and reporting. Based on the planned interim analysis, the IDMC concluded that the trial crossed the superiority boundary for its primary endpoint of iDFS and demonstrated a sustainable and clinically relevant treatment effect for Lynparza versus placebo.
