Results from the OlympiA Phase III trial showed olaparib (Lynparza) demonstrated a statistically significant and clinically meaningful improvement in invasive disease-free survival versus placebo in the adjuvant treatment of patients with germline BRCA-mutated high-risk human epidermal growth factor receptor 2-negative early breast cancer.
Upon review of the planned interim analysis in February 2021, the IDMC concluded that the trial had crossed the superiority boundary for its primary endpoint and recommended for the OlympiA trial to move early to primary analysis and reporting.
Lynparza is sponsored by AstraZeneca.
Results of this analysis will be presented during the plenary session of the 2021 American Society of Clinical Oncology Annual Meeting (abstract LBA#1). The results are being made available by ASCO on June 3 and simultaneously published in The New England Journal of Medicine prior to their presentation in the plenary session.
An estimated 2.3 million people were diagnosed with breast cancer worldwide in 2020, and BRCA1 and BRCA2 mutations are found in approximately 5% of breast cancer patients.
In the overall trial population of patients who had completed local treatment and standard neoadjuvant or adjuvant chemotherapy, results showed olaparib (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; p<0.0001). At three years, 85.9% of patients treated with olaparib (Lynparza) remained alive and free of invasive breast cancer and second cancers versus 77.1% on placebo.
Olaparib (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. Olaparib (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; p<0.0001). At the time of this initial data cut-off, fewer deaths had occurred in patients receiving olaparib (Lynparza), but the difference in overall survival (OS) did not reach statistical significance. The trial will continue to assess OS as a secondary endpoint.
“We are thrilled that our global academic and industry partnership has been able to help identify a possible new treatment for women with early-stage breast cancer who have mutations in their BRCA1 or BRCA2 genes,” OlympiA Steering Committee Chair Andrew Tutt, professor of oncology at The Institute of Cancer Research, London, and King’s College London, said in a statement. “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.”
“Women with early-stage breast cancer who have inherited BRCA mutations are typically diagnosed at a younger age. Up to now, there has been no treatment that specifically targets these mutations to reduce the risk of recurrence beyond the standard treatments available for early breast cancer. This major international study coordinated by the Breast International Group shows that giving olaparib for a year after completion of chemotherapy to patients with BRCA1 and 2 mutations increases the chances that they will remain free of invasive or metastatic cancer. These results reinforce how collaborative cancer research deepens our understanding of treating familial cancers and shows the value of testing for these mutations in patients with early breast cancer.”
“OlympiA represents a remarkable and successful global collaboration between leading international academic breast cancer research groups, cancer genetics experts, the National Cancer Institute and pharmaceutical industry partners to evaluate the efficacy and safety of olaparib to address the unmet need for improved therapy for individuals with high risk, inherited BRCA mutation-associated early breast cancer,” Charles Geyer, co-chair of the OlympiA Steering Committee, professor, and deputy director of the Houston Methodist Cancer Center, said in a statement.
“The results of OlympiA highlight the importance of inherited cancer genetic testing being widely available, as the results have become essential to modern oncology for targeted therapy decisions, now at breast cancer diagnosis as well as at presentation with metastatic disease,” Judy Garber, co-chair of the OlympiA Steering Committee, professor, and chief of the Division of Cancer Risk and Prevention, Dana-Farber Cancer Institute, said in a statement.
The safety and tolerability profile of olaparib (Lynparza) in this trial was in line with that observed in prior clinical trials.