{"entity":{"id":"paper-paola-1-nejm-2019","kind":"paper","name":"PAOLA-1: olaparib added to bevacizumab maintenance in newly diagnosed ovarian cancer, with benefit confined to HRD-positive tumours","aka":[],"tldr":"Adding the PARP inhibitor olaparib to bevacizumab after first-line chemotherapy for advanced ovarian cancer roughly doubled the time without progression in women whose tumours had defective DNA repair, but did nothing for those without it.","summary":"Double-blind, placebo-controlled phase 3 trial of 806 patients with newly diagnosed advanced high-grade ovarian cancer who had responded to platinum-taxane chemotherapy with bevacizumab, randomised 2:1 to two years of olaparib or placebo added to bevacizumab maintenance. Primary endpoint was investigator-assessed PFS.\n\nMedian PFS was 22.1 vs 16.6 months overall (HR 0.59), but 37.2 vs 17.7 months (HR 0.33) in homologous-recombination-deficient (HRD) tumours and no different in HRD-negative tumours (HR 1.00). The 2023 OS analysis showed a survival benefit in HRD-positive disease (5-year OS 65.5% vs 48.4%, HR 0.62). It established HRD testing as a decision tool and olaparib plus bevacizumab as a first-line maintenance standard for HRD-positive ovarian cancer.","asOf":"2026-09-08","links":[{"label":"NEJM 2019","url":"https://doi.org/10.1056/NEJMoa1911361"},{"label":"ClinicalTrials.gov NCT02477644","url":"https://clinicaltrials.gov/study/NCT02477644"}],"tags":[],"related":[],"cancers":["ovarian"],"sections":[],"technologies":["parp-inhibitor","hrd-testing","antiangiogenic","synthetic-lethality-approaches"],"targets":["parp","brca","vegf"],"drugs":["olaparib"],"companies":["astrazeneca","merck"],"institutions":["gemelli"],"pathways":[],"terms":["hrd","synthetic-lethality","pfs","os","germline-vs-somatic"],"trials":[],"people":["giovanni-scambia"],"bottlenecks":["b-biomarker-validation","b-dormancy-mrd","b-drug-pricing"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2019,"doi":"10.1056/NEJMoa1911361","authors":"Ray-Coquard I, Pautier P, Pignata S, et al.","paperType":"rct","findings":["Overall population: median PFS 22.1 vs 16.6 months; HR 0.59 (95% CI 0.49-0.72).","HRD-positive (including BRCA-mutated): median PFS 37.2 vs 17.7 months; HR 0.33.","HRD-positive without BRCA mutation: median PFS 28.1 vs 16.6 months; HR 0.43.","HRD-negative or unknown: no benefit (HR about 1.0).","Overall survival (Annals of Oncology 2023): HRD-positive 5-year OS 65.5% vs 48.4%, HR 0.62; no OS benefit in the ITT population (HR 0.92)."],"whatItMeans":"Women with newly diagnosed advanced ovarian cancer should have their tumour tested for BRCA mutations and homologous recombination deficiency, because those who are HRD-positive gain years of additional disease control and better survival from adding olaparib to bevacizumab maintenance. Those who are HRD-negative gain nothing from olaparib in this combination and should not be exposed to its toxicity and cost. HRD testing has become a routine part of ovarian cancer care as a result.","caveats":["HRD assays (Myriad myChoice and alternatives) have imperfect concordance and a substantial proportion of tests are inconclusive.","All patients received bevacizumab, so the trial cannot say whether olaparib alone would be as good in HRD-positive non-BRCA tumours (PRIMA suggests niraparib alone works).","No ITT overall survival benefit; the HRD-positive OS result is from a prespecified subgroup.","Two years of olaparib plus bevacizumab is expensive and adds anaemia, fatigue and nausea."],"changedPractice":true,"participants":806},"route":"/key-papers/paper-paola-1-nejm-2019/","neighbours":{"cancer":[{"id":"high-grade-serous-ovarian-cancer","kind":"cancer","name":"High-grade serous ovarian cancer","route":"/cancers/high-grade-serous-ovarian-cancer/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"platinum-sensitive-ovarian-cancer","kind":"cancer","name":"Platinum-sensitive ovarian cancer","route":"/cancers/platinum-sensitive-ovarian-cancer/"}],"technology":[{"id":"antiangiogenic","kind":"technology","name":"Anti-angiogenic therapy","route":"/technologies/antiangiogenic/"},{"id":"hrd-testing","kind":"technology","name":"HRD & BRCA testing","route":"/technologies/hrd-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/"},{"id":"vegf","kind":"target","name":"VEGF / VEGFR","route":"/targets/vegf/"}],"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/"}],"institution":[{"id":"gemelli","kind":"institution","name":"Policlinico Universitario A. Gemelli","route":"/institutions/gemelli/"}],"term":[{"id":"germline-vs-somatic","kind":"term","name":"Germline vs somatic mutations","route":"/terms/germline-vs-somatic/"},{"id":"hrd","kind":"term","name":"Homologous recombination deficiency (HRD)","route":"/terms/hrd/"},{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"},{"id":"synthetic-lethality","kind":"term","name":"Synthetic lethality","route":"/terms/synthetic-lethality/"}],"person":[{"id":"giovanni-scambia","kind":"person","name":"Giovanni Scambia","route":"/people/giovanni-scambia/"},{"id":"isabelle-ray-coquard","kind":"person","name":"Isabelle Ray-Coquard","route":"/people/isabelle-ray-coquard/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"},{"id":"b-drug-pricing","kind":"bottleneck","name":"Prices and value","route":"/bottlenecks/b-drug-pricing/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}