{"entity":{"id":"paper-pacific-nejm-2017","kind":"paper","name":"PACIFIC: a year of durvalumab after chemoradiotherapy for stage III lung cancer","aka":[],"tldr":"Giving the immunotherapy durvalumab for a year after chemoradiotherapy for unresectable stage III lung cancer tripled the time to progression and raised five-year survival from about a third to over 40%.","summary":"Double-blind, placebo-controlled phase 3 trial of 713 patients with unresectable stage III NSCLC who had not progressed after concurrent platinum-based chemoradiotherapy, randomised 2:1 to up to 12 months of durvalumab or placebo. Co-primary endpoints were PFS and overall survival.\n\nMedian PFS was 16.8 vs 5.6 months (HR 0.52) and overall survival was significantly improved (HR 0.68 in the 2018 report). Five-year OS was 42.9% vs 33.4%. It was the first change in stage III standard of care in two decades and the model for consolidation immunotherapy in small-cell lung cancer (ADRIATIC) and other tumours.","asOf":"2026-09-08","links":[{"label":"NEJM 2017","url":"https://doi.org/10.1056/NEJMoa1709937"},{"label":"NEJM 2018 (OS)","url":"https://doi.org/10.1056/NEJMoa1809697"},{"label":"ClinicalTrials.gov NCT02125461","url":"https://clinicaltrials.gov/study/NCT02125461"}],"tags":[],"related":["lung-cancer-evidence-roadmap","paper-spigel-pacific-five-year-survival-jco-2022","paper-lu-laura-osimertinib-stage-iii-nejm-2024"],"cancers":["nsclc","lung-cancer"],"sections":[],"technologies":["checkpoint-inhibitor","imrt-igrt","platinum"],"targets":["pdl1"],"drugs":["durvalumab"],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":["pfs","os","standard-of-care","irae"],"trials":[],"people":["cho-byoung-chul"],"bottlenecks":["b-immunotherapy-response","b-surgery-radiation-innovation","b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/NEJMoa1709937","authors":"Antonia SJ, Villegas A, Daniel D, et al.","paperType":"rct","findings":["Median PFS 16.8 vs 5.6 months; HR 0.52 (95% CI 0.42-0.65).","Overall survival (2018): HR 0.68; 24-month OS 66.3% vs 55.6%.","Five-year update (JCO 2022): OS 42.9% vs 33.4%; PFS 33.1% vs 19.0%.","Grade 3-4 pneumonitis or radiation pneumonitis 3.4% vs 2.6%; any-grade pneumonitis about 34% vs 25%.","Post hoc analysis suggested little benefit in PD-L1 below 1%, leading the EMA (but not FDA) to restrict the label to PD-L1 of 1% or more."],"whatItMeans":"Patients with stage III lung cancer that cannot be removed surgically should receive a year of durvalumab after completing chemoradiotherapy, provided they have not progressed. This roughly doubles the chance of being alive without progression at five years. Whether the benefit extends to PD-L1-negative tumours is contested, and the EGFR-mutated subgroup is better served by osimertinib (LAURA).","caveats":["PD-L1 status was not required for enrolment and the subgroup analysis by PD-L1 below 1% was unplanned and post hoc.","Patients had to have completed chemoradiotherapy without progression, a selected fitter population.","Combined radiation and immune pneumonitis requires careful monitoring, especially in Asian populations where rates were higher.","The trial did not test whether concurrent immunotherapy during radiotherapy is better; PACIFIC-2 was negative."],"changedPractice":true,"participants":713},"route":"/key-papers/paper-pacific-nejm-2017/","neighbours":{"roadmap":[{"id":"lung-cancer-evidence-roadmap","kind":"roadmap","name":"Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch","route":"/roadmaps/lung-cancer-evidence-roadmap/"}],"paper":[{"id":"paper-spigel-pacific-five-year-survival-jco-2022","kind":"paper","name":"Five-year survival outcomes from the PACIFIC trial: durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer","route":"/key-papers/paper-spigel-pacific-five-year-survival-jco-2022/"},{"id":"paper-lu-laura-osimertinib-stage-iii-nejm-2024","kind":"paper","name":"Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC","route":"/key-papers/paper-lu-laura-osimertinib-stage-iii-nejm-2024/"}],"cancer":[{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"stage-iii-unresectable-nsclc","kind":"cancer","name":"Unresectable stage III non-small-cell lung cancer","route":"/cancers/stage-iii-unresectable-nsclc/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"platinum","kind":"technology","name":"Platinum agents","route":"/technologies/platinum/"}],"target":[{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"}],"drug":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"}],"term":[{"id":"irae","kind":"term","name":"Immune-related adverse events (irAEs)","route":"/terms/irae/"},{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"},{"id":"standard-of-care","kind":"term","name":"Standard of care","route":"/terms/standard-of-care/"}],"person":[{"id":"cho-byoung-chul","kind":"person","name":"Byoung Chul Cho","route":"/people/cho-byoung-chul/"},{"id":"scott-antonia","kind":"person","name":"Scott J. Antonia","route":"/people/scott-antonia/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"},{"id":"b-surgery-radiation-innovation","kind":"bottleneck","name":"Surgery and radiotherapy cure most, get least","route":"/bottlenecks/b-surgery-radiation-innovation/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"trial":[{"id":"pacific","kind":"trial","name":"PACIFIC","route":"/trials/pacific/"}]}}