OlympiA: a year of olaparib after surgery for BRCA-mutated, high-risk early breast cancer
In women born with a BRCA1 or BRCA2 mutation whose early breast cancer was high risk, a year of the PARP inhibitor olaparib after standard treatment cut relapses by more than 40% and later improved survival.
Double-blind, placebo-controlled phase 3 trial of 1,836 patients with germline BRCA1/2 mutations and HER2-negative early breast cancer at high risk of recurrence, randomised to one year of olaparib or placebo after completing local therapy and chemotherapy. Primary endpoint was invasive disease-free survival.
Three-year iDFS was 85.9% vs 77.1% (HR 0.58) and distant disease-free survival 87.5% vs 80.4%. A 2022 update showed improved overall survival (HR 0.68). It was the first adjuvant PARP inhibitor and made germline testing part of treatment planning rather than only risk counselling.
- Three-year invasive disease-free survival 85.9% vs 77.1%, an 8.8-point gain; HR 0.58 (99.5% CI 0.41-0.82).
- Three-year distant disease-free survival 87.5% vs 80.4%; HR 0.57.
- Overall survival HR 0.68 at the second interim analysis (2022), with 4-year OS 89.8% vs 86.4%.
- Fewer new primary cancers, including ovarian, in the olaparib arm.
- Olaparib was generally well tolerated; anaemia was the main grade 3 toxicity and no excess of myelodysplasia or leukaemia was seen at this follow-up.
Everyone with HER2-negative early breast cancer that meets high-risk criteria should be offered germline BRCA testing, because a positive result now changes treatment: a year of olaparib after chemotherapy reduces relapse and death. It does not apply to low-risk tumours, HER2-positive disease, or somatic-only BRCA mutations.
- Most patients had not received platinum chemotherapy or pembrolizumab, so the benefit alongside the current KEYNOTE-522 regimen is extrapolated.
- Long-term risk of second haematological malignancies with PARP inhibitors needs continued surveillance.
- The hormone-receptor-positive subgroup was small (under a fifth of patients) and its benefit is less certain.
- Access to germline testing is uneven, particularly in lower-income settings.
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