{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T04:40:18Z","timestamp":1785386418397,"version":"3.55.0"},"reference-count":24,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"26","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2024,9,10]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> First-line therapy options in advanced cholangiocarcinoma (CCA) are based on the ABC-02 trial regimen (gemcitabine\/cisplatin [G\/C]). The NIFE trial examined nanoliposomal irinotecan\/fluorouracil\/leucovorin (nal-IRI\/FU\/LV) as alternative first-line therapy in advanced CCA. <\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p> NIFE is a prospective, open-label, randomized, multicenter phase II study that aimed at detecting efficacy comparable with the standard treatment. Patients with advanced CCA were randomly assigned (1:1) to receive nal-IRI\/FU\/LV (arm A) or G\/C (arm B). Stratification parameters were intrahepatic versus extrahepatic CCA, sex, and Eastern Cooperative Oncology Group (ECOG; 0\/1). Arm A was designed as a Simon's optimal two-stage design and arm B served as a randomized control group. The primary goal was to exclude an inferior progression-free survival (PFS) at 4 months of only 40%, while assuming a rate of 60% on G\/C population. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> Between 2018 and 2020, overall 91 patients were randomly assigned to receive nal-IRI\/FU\/LV (n = 49) or G\/C (n = 42). The NIFE trial formally met its primary end point with a 4-month PFS rate of 51% in patients receiving nal-IRI\/FU\/LV. The median PFS was 6 months (2.4-9.6) in arm A and 6.9 months (2.5-7.9) in arm B. Median overall survival (OS) was 15.9 months (10.6-20.3) in arm A and 13.6 months (6.5-17.7) in arm B. The exploratory comparison of study arms suggested a numerical but statistically not significant advantage for nal-IRI\/FU\/LV (hazard ratio for PFS, 0.85 [95% CI, 0.53 to 1.38] and for OS, 0.94 [95% CI, 0.58 to 1.50]). Analysis for stratification parameters revealed no differences for sex and ECOG, but for tumor localization. The objective response rate was 24.5% with nal-IRI\/FU\/LV and 11.9% with G\/C. No unexpected toxicities occurred. AEs related to nal-IRI\/FU\/LV were mainly GI and to G\/C hematologic. <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> Treatment of advanced CCA with nal-IRI\/FU\/LV demonstrated efficacy in first-line therapy without new safety findings and merits further validation. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.23.01566","type":"journal-article","created":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T19:59:34Z","timestamp":1717703974000},"page":"3094-3104","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":17,"title":["Nanoliposomal Irinotecan With Fluorouracil and Leucovorin or Gemcitabine Plus Cisplatin in Advanced Cholangiocarcinoma: A Phase II Study of the AIO Hepatobiliary-YMO Cancer Groups (NIFE-AIO-YMO HEP-0315)"],"prefix":"10.1200","volume":"42","clinical-trial-number":[{"clinical-trial-number":"nct03044587","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7654-2442","authenticated-orcid":false,"given":"Thomas J.","family":"Ettrich","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I, University of Ulm, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6853-0599","authenticated-orcid":false,"given":"Dominik P.","family":"Modest","sequence":"additional","affiliation":[{"name":"Hematology, Oncology and Tumor Immunology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7155-1278","authenticated-orcid":false,"given":"Marianne","family":"Sinn","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hematology and BMT with Division of Pneumology, University Hospital Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana K.","family":"Striefler","sequence":"additional","affiliation":[{"name":"Hematology, Oncology and Tumor Immunology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Opitz","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Hospital St Elisabeth and St Barbara Halle, Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Goetze","sequence":"additional","affiliation":[{"name":"Institute of Clinical Cancer Research (IKF) at Northwest Hospital, UCT-University Cancer Center, Frankfurt Am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eike","family":"Gallmeier","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Endocrinology, Philipps University Marburg, Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Angermeier","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hematology and Oncology, Ludwigsburg Hospital, Ludwigsburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludwig","family":"Fischer von Weikersthal","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, St Marien Hospital, Amberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutz","family":"Jacobasch","sequence":"additional","affiliation":[{"name":"Private Practice Oncology\/Hematology, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Waldschmidt","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hemato-Oncology, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Niedermeier","sequence":"additional","affiliation":[{"name":"Private Practice Oncology\/Hematology, Memmingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sohm","sequence":"additional","affiliation":[{"name":"Private Practice Oncology\/Hematology, Landshut, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas W.","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University of Ulm, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8032-8043","authenticated-orcid":false,"given":"Giulia","family":"Manzini","sequence":"additional","affiliation":[{"name":"Department of Visceral Surgery, Kantonsspital Aarau, Aarau, Swiss"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uli","family":"Fehrenbach","sequence":"additional","affiliation":[{"name":"Clinic for Radiology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo Alexander","family":"Auer","sequence":"additional","affiliation":[{"name":"Clinic for Radiology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4383-5716","authenticated-orcid":false,"given":"Clarissa","family":"Hosse","sequence":"additional","affiliation":[{"name":"Clinic for Radiology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Vogele","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Radiology, Ulm University Medical Center, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Disorn","family":"Sookthai","sequence":"additional","affiliation":[{"name":"Biostatistics\u2014Institute of Clinical Cancer Research (IKF) at Northwest Hospital, UCT-University Cancer Center, Frankfurt Am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Schaaf","sequence":"additional","affiliation":[{"name":"Biostatistics\u2014Institute of Clinical Cancer Research (IKF) at Northwest Hospital, UCT-University Cancer Center, Frankfurt Am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Muche","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6037-8836","authenticated-orcid":false,"given":"Axel","family":"Hinke","sequence":"additional","affiliation":[{"name":"Biostatistics, CCRC Cancer Clinical Research Consulting, Duesseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Seufferlein","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University of Ulm, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0484-0974","authenticated-orcid":false,"given":"Lukas","family":"Perkhofer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University of Ulm, Ulm, Germany"},{"name":"Institute of Molecular Oncology and Stem Cell Biology, Ulm University Hospital, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"b1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21387"},{"key":"b2","doi-asserted-by":"publisher","DOI":"10.3109\/00365521.2011.589472"},{"key":"b3","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2015-0446"},{"key":"b4","doi-asserted-by":"publisher","DOI":"10.1055\/a-1589-7585"},{"key":"b5","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw324"},{"key":"b6","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.00679"},{"key":"b7","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/1720696"},{"key":"b8","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00139-4"},{"key":"b9","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00409-5"},{"key":"b10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2019.10.004"},{"key":"b11","doi-asserted-by":"publisher","DOI":"10.1056\/EVIDoa2200015"},{"key":"b12","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00727-4"},{"key":"b13","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.720"},{"key":"b14","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdt002"},{"key":"b15","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00486-1"},{"key":"b16","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6603648"},{"key":"b17","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.736113"},{"key":"b18","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0908721"},{"key":"b19","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30109-1"},{"key":"b20","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30157-1"},{"key":"b21","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2021.3836"},{"key":"b22","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00336-3"},{"key":"b23","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30321-1"},{"key":"b24","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00986-1"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.23.01566","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T22:01:46Z","timestamp":1725573706000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.23.01566"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,10]]},"references-count":24,"journal-issue":{"issue":"26","published-print":{"date-parts":[[2024,9,10]]}},"alternative-id":["10.1200\/JCO.23.01566"],"URL":"https:\/\/doi.org\/10.1200\/jco.23.01566","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,10]]},"assertion":[{"value":"2023-07-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-03","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}