{"entity":{"id":"polo","kind":"trial","name":"POLO","aka":[],"tldr":"The first biomarker-directed drug approval in pancreatic cancer, for the roughly 5-7% with inherited BRCA mutations, though it did not extend overall survival.","summary":"POLO, trial NCT02184195 sponsored by AstraZeneca and Merck and reported in 2019, produced the first biomarker-directed drug approval in pancreatic cancer, for the roughly five to seven percent of patients with inherited BRCA mutations, though it did not extend overall survival. It randomised 154 patients with germline BRCA-mutated metastatic disease that had not progressed on at least sixteen weeks of platinum chemotherapy to olaparib maintenance or placebo, met its primary progression-free survival endpoint and led to FDA approval in December 2019, but overall survival was no different. OnCo links it to PARP inhibitors and germline testing, to BRCA1 and BRCA2 and PARP as targets. It is a single pivotal trial with no confirmatory study, and whether a progression benefit alone justifies maintenance is the open question.","status":"mixed","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT02184195","url":"https://clinicaltrials.gov/study/NCT02184195"},{"label":"Lynparza label (openFDA): POLO study section","url":"https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22LYNPARZA%22"},{"label":"Kindler et al., POLO overall survival (JCO 2022)","url":"https://doi.org/10.1200/JCO.21.01604"}],"tags":[],"related":[],"cancers":["pancreatic","brca-palb2-pdac"],"sections":[],"technologies":["parp-inhibitor","germline-testing"],"targets":["brca","parp"],"drugs":["olaparib"],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":[],"trials":["panoptimox-prodige-35","nct05093231"],"people":["talia-golan","hedy-kindler"],"bottlenecks":[],"keyPapers":["paper-golan-brca-pancreatic-platinum-survival-bjc-2014","paper-park-hrd-pancreatic-platinum-ccr-2020"],"journals":[],"dependsOn":[],"notes":["Design (NEJM 2019): 3,315 patients screened for a germline BRCA mutation to randomise 154 (92 olaparib 300 mg twice daily, 62 placebo) at sites in 12 countries including nine in the UK (Edinburgh, Glasgow, Liverpool, London, Manchester, Northwood, Nottingham, Surrey); 75 percent had received FOLFIRINOX, 30 percent carried BRCA1 and 69 percent BRCA2 (label). Final overall survival (JCO 2022): 19.0 against 19.2 months (hazard ratio 0.83, 0.56 to 1.22; p 0.3487), curves separating at about 24 months with three-year survival 33.9 against 17.8 percent; time to first subsequent therapy or death hazard ratio 0.44 and to second subsequent therapy 0.61 favoured olaparib; grade 3 or worse adverse events 40 against 23 percent in the primary report. Regulators: FDA approval December 2019 (Lynparza label indication 1.6); EU indication listed; NICE appraisal TA750 terminated on 8 December 2021 without a company submission."],"nct":"NCT02184195","phase":"3","setting":"Germline BRCA-mutated metastatic PDAC not progressed on ≥16 weeks of platinum: olaparib maintenance vs placebo","sponsor":"AstraZeneca / Merck","result":"PFS HR 0.53; OS HR 0.83 (not significant).","started":"2014-12-16","startedType":"actual","yearReported":2019,"enrolled":154,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival","primary":true,"unit":"months","arms":[{"name":"Olaparib maintenance","n":92,"value":7.4},{"name":"Placebo","n":62,"value":3.8}],"hr":0.53,"ci":[0.35,0.82],"p":"0.004","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa1903387"},{"endpoint":"Overall survival","unit":"months","arms":[{"name":"Olaparib maintenance","value":19,"note":"Not significant"},{"name":"Placebo","value":19.2}],"hr":0.83,"source":"https://ascopubs.org/doi/10.1200/JCO.21.01604"}],"replication":"Single pivotal trial; PFS but not OS. No confirmatory trial."},"route":"/trials/polo/","neighbours":{"cancer":[{"id":"brca-palb2-pdac","kind":"cancer","name":"BRCA or PALB2-mutant pancreatic ductal adenocarcinoma","route":"/cancers/brca-palb2-pdac/"},{"id":"metastatic-pdac","kind":"cancer","name":"Metastatic pancreatic ductal adenocarcinoma","route":"/cancers/metastatic-pdac/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"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/"}],"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/"}],"trial":[{"id":"panoptimox-prodige-35","kind":"trial","name":"PANOPTIMOX-PRODIGE 35","route":"/trials/panoptimox-prodige-35/"},{"id":"nct05093231","kind":"trial","name":"Pembrolizumab With Olaparib as Combined Therapy in Metastatic Pancreatic Cancer","route":"/trials/nct05093231/"}],"person":[{"id":"hedy-kindler","kind":"person","name":"Hedy L. Kindler","route":"/people/hedy-kindler/"},{"id":"talia-golan","kind":"person","name":"Talia Golan","route":"/people/talia-golan/"}],"paper":[{"id":"paper-park-hrd-pancreatic-platinum-ccr-2020","kind":"paper","name":"Genomic methods identify homologous recombination deficiency in pancreas adenocarcinoma and optimize treatment selection","route":"/key-papers/paper-park-hrd-pancreatic-platinum-ccr-2020/"},{"id":"paper-asco-metastatic-pancreatic-cancer-guideline-update-jco-2020","kind":"paper","name":"Metastatic Pancreatic Cancer: ASCO Guideline Update","route":"/key-papers/paper-asco-metastatic-pancreatic-cancer-guideline-update-jco-2020/"},{"id":"paper-golan-brca-pancreatic-platinum-survival-bjc-2014","kind":"paper","name":"Overall survival and clinical characteristics of pancreatic cancer in BRCA mutation carriers","route":"/key-papers/paper-golan-brca-pancreatic-platinum-survival-bjc-2014/"},{"id":"paper-esmo-pancreatic-cancer-guideline-ann-oncol-2023","kind":"paper","name":"Pancreatic cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","route":"/key-papers/paper-esmo-pancreatic-cancer-guideline-ann-oncol-2023/"},{"id":"paper-polo-overall-survival-olaparib-gbrca-pancreatic-jco-2022","kind":"paper","name":"POLO final overall survival: maintenance olaparib versus placebo in germline BRCA-mutated metastatic pancreatic cancer","route":"/key-papers/paper-polo-overall-survival-olaparib-gbrca-pancreatic-jco-2022/"},{"id":"paper-polo-olaparib-maintenance-gbrca-pancreatic-nejm-2019","kind":"paper","name":"POLO: maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer","route":"/key-papers/paper-polo-olaparib-maintenance-gbrca-pancreatic-nejm-2019/"}],"roadmap":[{"id":"pancreatic-roadmap","kind":"roadmap","name":"Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question","route":"/roadmaps/pancreatic-roadmap/"}]}}