{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T20:37:42Z","timestamp":1793911062826,"version":"4.8.0"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>FOLFOX (folinic acid, 5\u2010fluorouracil, oxaliplatin) is the standard second\u2010line treatment in patients with biliary tract cancer (BTC) not eligible for targeted therapies. FOLFIRI (folinic acid, 5\u2010fluorouracil, irinotecan) is a frequently adopted alternative combination in clinical practice, especially in patients primarily refractory to platinum\u2010based first\u2010line treatment. However, a real\u2010world direct comparison between the two regimens has not yet been reported.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a multicenter, retrospective analysis comparing patients with advanced BTC treated with cisplatin\u2010gemcitabine, with or without durvalumab, as first\u2010line and FOLFIRI or FOLFOX as second\u2010line therapy. The primary endpoints were overall survival (OS) and progression free survival (PFS), as evaluated from the start of second\u2010line, according to the chosen regimen. Multivariable models were tested, also considering prior cisplatin sensitivity and BRCAness status according to tumour molecular profiling. Clinical differences between the FOLFOX and FOLFIRI arms were balanced through inverse probability of treatment weighting (IPTW) methodology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 259 patients were included, of whom 109 were treated with FOLFOX and 150 with FOLFIRI. Patient and tumour characteristics were overall balanced between the two arms. No significant difference between FOLFIRI and FOLFOX was observed in terms of PFS (median 3.1 vs. 3.5\u2009months, HR 1.01; IPTW\u2010adjusted median 3.2 vs. 3.5\u2009months, HR 0.86) or OS (median 9.9 vs. 9.0\u2009months, HR 1.09; IPTW\u2010adjusted median 10.0 vs. 8.9\u2009months, HR 1.04), with platinum sensitivity and BRCAness status emerging as independent prognostic factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>FOLFOX and FOLFIRI showed modest, comparable efficacy as second\u2010line regimens in patients with BTC pretreated with cisplatin\u2010gemcitabine, with platinum\u2010sensitive patients experiencing significantly longer PFS and OS, independently of the chosen second\u2010line regimen.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70502","type":"journal-article","created":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T16:13:39Z","timestamp":1767111219000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>FOLFOX<\/scp>\n                    Versus\n                    <scp>FOLFIRI<\/scp>\n                    as Second\u2010Line Chemotherapy in Patients With Advanced Biliary Tract Cancers: A Multicenter, Italian Study"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8173-824X","authenticated-orcid":false,"given":"Chiara","family":"Pircher","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Dei Tumori  Milan 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