What is the Olympia trial for breast cancer?

From the Guidelines

The Olympia trial is a clinical trial for patients with germline BRCA1 or BRCA2 mutations and high-risk, early-stage breast cancer, investigating the efficacy of olaparib, a PARP inhibitor, as an adjuvant treatment to reduce the risk of breast cancer recurrence 1.

Key Features of the Trial

• The trial evaluates the efficacy of adjuvant PARP inhibitor therapy with olaparib in patients with early-stage, HER2-negative breast cancer with high risk of recurrence and germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants 1.
• Patients in the trial receive olaparib for one year, with the primary goal of assessing whether olaparib can improve invasive disease-free survival compared to placebo in this high-risk population 1.
• The trial has shown that olaparib can improve invasive disease-free survival, with a 3-year invasive disease-free survival rate of 85.9% in the olaparib group compared to 77.1% in the placebo group (HR, 0.58 [99.5% CI, 0.41 to 0.82]; P < .001) 1.
• The trial has also shown that olaparib can improve distant disease-free survival, with a 3-year distant disease-free survival rate of 87.5% in the olaparib group compared to 80.4% in the placebo group (HR, 0.57 [99.5% CI, 0.39 to 0.83]; P < .001) 1.

Patient Eligibility

• Patients with germline BRCA1 or BRCA2 mutations and high-risk, early-stage breast cancer are eligible for the trial 1.
• High-risk features include stages 2 and 3, TNBC with residual disease after pre-operative chemotherapy, or node-positive or pT2 irrespective of nodal status or ER+ disease with four or more involved lymph nodes or significant residual disease after pre-operative chemotherapy 1.

Treatment and Outcomes

• Patients in the trial receive olaparib 300mg orally twice daily for one year 1.
• The primary outcome of the trial is invasive disease-free survival, with secondary outcomes including distant disease-free survival and overall survival 1.
• The trial has shown that olaparib can improve invasive disease-free survival and distant disease-free survival, with a trend towards improved overall survival 1.

From the Research

Overview of the Olympia Trial

• The Olympia trial is a randomized, double-blind trial that compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC) 2.
• The trial demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS) with olaparib compared to placebo 2.
• The second pre-specified interim analysis of overall survival (OS) showed significant improvement in the olaparib group relative to the placebo group, with a hazard ratio of 0.68 and a 4-year OS of 89.8% in the olaparib group versus 86.4% in the placebo group 2.

Patient Eligibility and Outcomes

• The Olympia trial included patients with gBRCA1/2pv and high-risk, HER2-negative EBC, who had received (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated 2.
• The trial showed that olaparib was beneficial across major subgroups, including those with hormone receptor-positive and triple-negative breast cancer 2, 3.
• The 4-year IDFS and DDFS rates were 82.7% and 86.5%, respectively, in the olaparib group, compared to 75.4% and 79.1% in the placebo group 2.

Comparison to Other Studies

• The OlympiAD trial, which compared olaparib to chemotherapy treatment of physician's choice in patients with gBRCAm and HER2-negative metastatic breast cancer, showed that olaparib significantly prolonged progression-free survival, but did not demonstrate a statistically significant improvement in OS 4, 5.
• A real-world study using data from a population-based registry found that 14.2% of patients with HER2-negative EBC were classified as "high risk" according to the Olympia criteria, and that these patients had a worse 10-year overall survival rate compared to those who were not classified as "high risk" 6.