# OlympiA: a year of olaparib after surgery for BRCA-mutated, high-risk early breast cancer

Source: https://onco.cc/key-papers/paper-olympia-nejm-2021/  
OnCo record `paper-olympia-nejm-2021` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2021
- DOI: 10.1056/NEJMoa2105215
- Authors: Tutt ANJ, Garber JE, Kaufman B, et al.
- Findings: 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.
- What it means: 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.
- Caveats: 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.

## Sources

- NEJM 2021: https://doi.org/10.1056/NEJMoa2105215
- ClinicalTrials.gov NCT02032823: https://clinicaltrials.gov/study/NCT02032823

## Connected records

- cancers: [Early triple-negative breast cancer](https://onco.cc/cancers/tnbc-early/), [High-risk early HR-positive breast cancer](https://onco.cc/cancers/hr-positive-early-high-risk/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/), [PARP inhibitors](https://onco.cc/technologies/parp-inhibitor/), [Synthetic lethality approaches](https://onco.cc/technologies/synthetic-lethality-approaches/)
- targets: [BRCA1 / BRCA2 (HRD)](https://onco.cc/targets/brca/), [PARP](https://onco.cc/targets/parp/)
- drugs: [Olaparib](https://onco.cc/drugs/olaparib/)
- companies: [AstraZeneca](https://onco.cc/companies/astrazeneca/), [Merck & Co. (MSD)](https://onco.cc/companies/merck/)
- terms: [Germline vs somatic mutations](https://onco.cc/terms/germline-vs-somatic/), [Neoadjuvant / adjuvant / perioperative](https://onco.cc/terms/neoadjuvant-adjuvant/), [Residual cancer burden (RCB)](https://onco.cc/terms/rcb/), [Synthetic lethality](https://onco.cc/terms/synthetic-lethality/)
- trials: [OlympiA](https://onco.cc/trials/olympia/)
- people: [Andrew Tutt](https://onco.cc/people/andrew-tutt/), [Charles E. Geyer Jr.](https://onco.cc/people/charles-geyer/), [Evandro de Azambuja](https://onco.cc/people/evandro-de-azambuja/), [Judy E. Garber](https://onco.cc/people/judy-garber/), [Martine Piccart](https://onco.cc/people/martine-piccart/), [Sibylle Loibl](https://onco.cc/people/sibylle-loibl/), [Susan M. Domchek](https://onco.cc/people/susan-domchek/), [Zhi-Ming Shao](https://onco.cc/people/shao-zhi-ming/)
- bottlenecks: [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/), [Inherited risk is mostly unidentified](https://onco.cc/bottlenecks/b-hereditary-risk/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- key papers: [Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer](https://onco.cc/key-papers/paper-olympia-overall-survival-ann-oncol-2022/)
- roadmaps: [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/)

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