{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T01:07:14Z","timestamp":1789175234308,"version":"build-2803163510"},"reference-count":21,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100017655","name":"Incyte","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017655","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2026,8]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background & Aims<\/jats:title>\n \n Anti\u2010FGFR therapies changed the treatment landscape for patients with previously treated, advanced, or metastatic cholangiocarcinoma (CCA) harbouring\n FGFR2<\/jats:italic>\n fusions\/rearrangements. However, primary resistance to FGFR inhibitors remains a key challenge. In the present real\u2010world study, we aimed to evaluate the prognostic impact of concomitant GAs in patients with\n FGFR2<\/jats:italic>\n \u2010positive CCA treated with pemigatinib.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This study included PEMIREAL\u2010PEMIBIL patients treated with pemigatinib in second or later lines. Only patients who underwent extensive DNA\u2010 and\/or RNA\u2010based next\u2010generation sequencing (NGS) analysis were considered. Primary endpoint was progression\u2010free survival (PFS), with overall response rate, disease control rate and overall survival (OS) as secondary endpoint. OS and PFS were calculated by Kaplan\u2013Meier and log\u2010rank test. Multivariate analysis used cox\u2010regression model. Level of statistical significance\n p<\/jats:italic>\n was 0.05.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of 72 patients of PEMIREAL\u2010PEMIBIL, 63 patients had evaluable NGS data, with concomitant GAs identified in 28 patients (44.4%). The most frequently observed concomitant GAs involved\n BAP1<\/jats:italic>\n (7\/63, 11.1%),\n CDKN2A<\/jats:italic>\n (7\/63, 11.1%),\n TP53<\/jats:italic>\n (6\/63, 9.5%),\n CDKN2B<\/jats:italic>\n (5\/63, 7.9%),\n PTEN<\/jats:italic>\n (3\/63, 4.7%) and\n IDH1<\/jats:italic>\n (1\/63, 1.5%). A significantly shorter PFS was observed in patients with\n CDKN2A<\/jats:italic>\n mutations compared to\n CDKN2A<\/jats:italic>\n wild\u2010type tumours (4.79 vs. 8.66\u2009months,\n p<\/jats:italic>\n \u2009=\u20090.0011, HR: 3.48 95% CI: 0.91\u201313.24), and similarly in patients with\n BAP1<\/jats:italic>\n mutations compared to\n BAP1<\/jats:italic>\n wild\u2010type tumours (5.97 vs. 8.52\u2009months,\n p<\/jats:italic>\n \u2009=\u20090.025, HR:2.55 95% CI: 0.72\u20139.00). No significant differences in OS were observed.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Our results support the negative prognostic role of\n BAP1<\/jats:italic>\n and\n CDKN2A<\/jats:italic>\n GAs on PFS in patients with locally advanced or metastatic CCA with\n FGFR2<\/jats:italic>\n gene fusion\/rearrangement treated with pemigatinib in a real\u2010world setting.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/liv.70813","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T07:18:12Z","timestamp":1784877492000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic Impact of Concomitant Genomic Alterations in\n FGFR2<\/scp>\n \u2010Positive Cholangiocarcinoma Treated With Pemigatinib"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2874-6029","authenticated-orcid":false,"given":"Carolina","family":"Liguori","sequence":"first","affiliation":[{"name":"Clinica Oncologica e Centro Regionale di Genetica Oncologica Universit\u00e0 Politecnica delle Marche, Azienda Ospedaliero\u2010Universitaria delle Marche Ancona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7344-0590","authenticated-orcid":false,"given":"Riccardo","family":"Giampieri","sequence":"additional","affiliation":[{"name":"Clinica Oncologica e Centro Regionale di Genetica Oncologica Universit\u00e0 Politecnica delle Marche, Azienda Ospedaliero\u2010Universitaria delle Marche Ancona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blandine","family":"Delaunay","sequence":"additional","affiliation":[{"name":"Digestive Oncology Department Centre Hospitalier Universitaire de Toulouse \u2013 Hopital Rangueil Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9395-2104","authenticated-orcid":false,"given":"Giada","family":"Pinterpe","sequence":"additional","affiliation":[{"name":"Clinica Oncologica e Centro Regionale di Genetica Oncologica Universit\u00e0 Politecnica delle Marche, Azienda Ospedaliero\u2010Universitaria delle Marche Ancona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5207-3672","authenticated-orcid":false,"given":"Adelaide","family":"Mazzocca","sequence":"additional","affiliation":[{"name":"Clinica Oncologica e Centro Regionale di Genetica Oncologica Universit\u00e0 Politecnica delle Marche, Azienda Ospedaliero\u2010Universitaria delle Marche Ancona 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