{"entity":{"id":"paper-olympia-nejm-2021","kind":"paper","name":"OlympiA: a year of olaparib after surgery for BRCA-mutated, high-risk early breast cancer","aka":[],"tldr":"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.\n\nThree-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.","asOf":"2026-09-08","links":[{"label":"NEJM 2021","url":"https://doi.org/10.1056/NEJMoa2105215"},{"label":"ClinicalTrials.gov NCT02032823","url":"https://clinicaltrials.gov/study/NCT02032823"}],"tags":[],"related":[],"cancers":["tnbc","breast-hr-positive"],"sections":[],"technologies":["parp-inhibitor","germline-testing","synthetic-lethality-approaches"],"targets":["parp","brca"],"drugs":["olaparib"],"companies":["astrazeneca","merck"],"institutions":[],"pathways":[],"terms":["germline-vs-somatic","synthetic-lethality","neoadjuvant-adjuvant","rcb"],"trials":["olympia"],"people":["andrew-tutt","judy-garber","evandro-de-azambuja","susan-domchek","shao-zhi-ming","sibylle-loibl","martine-piccart","charles-geyer"],"bottlenecks":["b-hereditary-risk","b-dormancy-mrd"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2021,"doi":"10.1056/NEJMoa2105215","authors":"Tutt ANJ, Garber JE, Kaufman B, et al.","paperType":"rct","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."],"whatItMeans":"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."],"changedPractice":true,"participants":1836},"route":"/key-papers/paper-olympia-nejm-2021/","neighbours":{"cancer":[{"id":"tnbc-early","kind":"cancer","name":"Early triple-negative breast cancer","route":"/cancers/tnbc-early/"},{"id":"hr-positive-early-high-risk","kind":"cancer","name":"High-risk early HR-positive breast cancer","route":"/cancers/hr-positive-early-high-risk/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"germline-testing","kind":"technology","name":"Germline (hereditary) testing","route":"/technologies/germline-testing/"},{"id":"parp-inhibitor","kind":"technology","name":"PARP inhibitors","route":"/technologies/parp-inhibitor/"},{"id":"synthetic-lethality-approaches","kind":"technology","name":"Synthetic lethality approaches","route":"/technologies/synthetic-lethality-approaches/"}],"target":[{"id":"brca","kind":"target","name":"BRCA1 / BRCA2 (HRD)","route":"/targets/brca/"},{"id":"parp","kind":"target","name":"PARP","route":"/targets/parp/"}],"drug":[{"id":"olaparib","kind":"drug","name":"Olaparib","route":"/drugs/olaparib/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"},{"id":"merck","kind":"company","name":"Merck & Co. (MSD)","route":"/companies/merck/"}],"term":[{"id":"germline-vs-somatic","kind":"term","name":"Germline vs somatic mutations","route":"/terms/germline-vs-somatic/"},{"id":"neoadjuvant-adjuvant","kind":"term","name":"Neoadjuvant / adjuvant / perioperative","route":"/terms/neoadjuvant-adjuvant/"},{"id":"rcb","kind":"term","name":"Residual cancer burden (RCB)","route":"/terms/rcb/"},{"id":"synthetic-lethality","kind":"term","name":"Synthetic lethality","route":"/terms/synthetic-lethality/"}],"trial":[{"id":"olympia","kind":"trial","name":"OlympiA","route":"/trials/olympia/"}],"person":[{"id":"andrew-tutt","kind":"person","name":"Andrew Tutt","route":"/people/andrew-tutt/"},{"id":"charles-geyer","kind":"person","name":"Charles E. Geyer Jr.","route":"/people/charles-geyer/"},{"id":"evandro-de-azambuja","kind":"person","name":"Evandro de Azambuja","route":"/people/evandro-de-azambuja/"},{"id":"judy-garber","kind":"person","name":"Judy E. Garber","route":"/people/judy-garber/"},{"id":"martine-piccart","kind":"person","name":"Martine Piccart","route":"/people/martine-piccart/"},{"id":"sibylle-loibl","kind":"person","name":"Sibylle Loibl","route":"/people/sibylle-loibl/"},{"id":"susan-domchek","kind":"person","name":"Susan M. Domchek","route":"/people/susan-domchek/"},{"id":"shao-zhi-ming","kind":"person","name":"Zhi-Ming Shao","route":"/people/shao-zhi-ming/"}],"bottleneck":[{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"},{"id":"b-hereditary-risk","kind":"bottleneck","name":"Inherited risk is mostly unidentified","route":"/bottlenecks/b-hereditary-risk/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"paper":[{"id":"paper-olympia-overall-survival-ann-oncol-2022","kind":"paper","name":"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","route":"/key-papers/paper-olympia-overall-survival-ann-oncol-2022/"}],"roadmap":[{"id":"tnbc-roadmap","kind":"roadmap","name":"Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem","route":"/roadmaps/tnbc-roadmap/"}]}}