{"entity":{"id":"paper-solo-1-nejm-2018","kind":"paper","name":"SOLO-1: two years of olaparib maintenance after first-line chemotherapy for BRCA-mutated ovarian cancer","aka":[],"tldr":"In women with newly diagnosed advanced BRCA-mutated ovarian cancer who had responded to chemotherapy, two years of the PARP inhibitor olaparib kept far more of them free of progression than placebo, and the effect persisted for years after the tablets stopped. It moved PARP inhibitors into first-line maintenance and made BRCA testing at diagnosis routine.","summary":"Double-blind, placebo-controlled phase 3 trial of 391 patients with newly diagnosed advanced high-grade ovarian cancer and a BRCA1/2 mutation who had responded to platinum-based chemotherapy, randomised 2:1 to two years of olaparib or placebo maintenance. Primary endpoint was investigator-assessed PFS.\n\nPFS HR was 0.30, with 3-year PFS 60% vs 27%. Long-term follow-up showed a durable effect after treatment stopped: 7-year OS 67% vs 46.5% (HR 0.55) and about 45% of olaparib patients progression-free at seven years, suggesting a fraction were cured. It moved PARP inhibitors from recurrent disease to first-line maintenance and made BRCA testing at diagnosis mandatory.","asOf":"2026-09-08","links":[{"label":"NEJM 2018","url":"https://doi.org/10.1056/NEJMoa1810858"},{"label":"ClinicalTrials.gov NCT01844986","url":"https://clinicaltrials.gov/study/NCT01844986"}],"tags":[],"related":[],"cancers":["ovarian"],"sections":[],"technologies":["parp-inhibitor","germline-testing","synthetic-lethality-approaches"],"targets":["parp","brca"],"drugs":["olaparib"],"companies":["astrazeneca","merck"],"institutions":[],"pathways":[],"terms":["synthetic-lethality","pfs","os","germline-vs-somatic","hrd"],"trials":[],"people":["giovanni-scambia","amit-oza"],"bottlenecks":["b-hereditary-risk","b-dormancy-mrd","b-resistance"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/NEJMoa1810858","authors":"Moore K, Colombo N, Scambia G, et al.","paperType":"rct","findings":["Progression-free survival HR 0.30 (95% CI 0.23-0.41); 3-year PFS 60% vs 27%.","Median PFS 56.0 vs 13.8 months at five-year follow-up (Lancet Oncology 2021); 5-year PFS 48% vs 21%.","Overall survival at seven years (JCO 2023): 67.0% vs 46.5%; HR 0.55 (95% CI 0.40-0.76), despite 44% of placebo patients later receiving a PARP inhibitor.","Grade 3 or higher adverse events 39% vs 18%, mainly anaemia; 12% discontinued olaparib for toxicity.","Myelodysplastic syndrome or acute myeloid leukaemia in about 1.5% of olaparib patients at long follow-up, similar to placebo."],"whatItMeans":"Every woman diagnosed with advanced high-grade ovarian cancer should be tested for BRCA mutations at diagnosis, because those who carry one should receive two years of olaparib after chemotherapy, which greatly extends the time in remission and improves long-term survival. The plateau in the survival curves suggests some patients are cured by this approach. Toxicity is mostly anaemia, fatigue and nausea, and the two-year limit appears sufficient.","caveats":["The OS analysis did not formally meet its stringent statistical threshold (p<0.0001) though the effect is large and consistent.","Only BRCA-mutated patients; PRIMA and PAOLA-1 extended maintenance PARP inhibition to HRD-positive non-BRCA tumours.","Long-term surveillance for secondary leukaemia is warranted.","Patients who progress on a PARP inhibitor respond poorly to subsequent platinum, complicating later treatment."],"changedPractice":true,"participants":391},"route":"/key-papers/paper-solo-1-nejm-2018/","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":"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":"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":"amit-oza","kind":"person","name":"Amit M. Oza","route":"/people/amit-oza/"},{"id":"giovanni-scambia","kind":"person","name":"Giovanni Scambia","route":"/people/giovanni-scambia/"},{"id":"kathleen-moore","kind":"person","name":"Kathleen N. Moore","route":"/people/kathleen-moore/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"},{"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/"}],"idea":[{"id":"idea-ctdna-guided-parp-duration","kind":"idea","name":"ctDNA-guided duration of PARP maintenance","route":"/ideas/idea-ctdna-guided-parp-duration/"}]}}