Prognostic Impact of Concomitant Genomic Alterations in <scp>FGFR2</scp> ‐Positive Cholangiocarcinoma Treated With Pemigatinib

BACKGROUND & AIMS: Anti-FGFR therapies changed the treatment landscape for patients with previously treated, advanced, or metastatic cholangiocarcinoma (CCA) harbouring FGFR2 fusions/rearrangements. However, primary resistance to FGFR inhibitors remains a key challenge. In the present real-world study, we aimed to evaluate the prognostic impact of concomitant GAs in patients with FGFR2-positive CCA treated with pemigatinib. METHODS: This study included PEMIREAL-PEMIBIL patients treated with pemigatinib in second or later lines. Only patients who underwent extensive DNA- and/or RNA-based next-generation sequencing (NGS) analysis were considered. Primary endpoint was progression-free survival (PFS), with overall response rate, disease control rate and overall survival (OS) as secondary endpoint. OS and PFS were calculated by Kaplan-Meier and log-rank test. Multivariate analysis used cox-regression model. Level of statistical significance p was 0.05. RESULTS: Of 72 patients of PEMIREAL-PEMIBIL, 63 patients had evaluable NGS data, with concomitant GAs identified in 28 patients (44.4%). The most frequently observed concomitant GAs involved BAP1 (7/63, 11.1%), CDKN2A (7/63, 11.1%), TP53 (6/63, 9.5%), CDKN2B (5/63, 7.9%), PTEN (3/63, 4.7%) and IDH1 (1/63, 1.5%). A significantly shorter PFS was observed in patients with CDKN2A mutations compared to CDKN2A wild-type tumours (4.79 vs. 8.66 months, p = 0.0011, HR: 3.48 95% CI: 0.91-13.24), and similarly in patients with BAP1 mutations compared to BAP1 wild-type tumours (5.97 vs. 8.52 months, p = 0.025, HR:2.55 95% CI: 0.72-9.00). No significant differences in OS were observed. CONCLUSIONS: Our results support the negative prognostic role of BAP1 and CDKN2A GAs on PFS in patients with locally advanced or metastatic CCA with FGFR2 gene fusion/rearrangement treated with pemigatinib in a real-world setting.

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Journal
Liver International
Published
2026-07-24
DOI
https://doi.org/10.1111/liv.70813
Primary Topic
Cholangiocarcinoma and Gallbladder Cancer Studies
Type
article
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0.00

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article

Prognostic Impact of Concomitant Genomic Alterations in FGFR2 ‐Positive Cholangiocarcinoma Treated With Pemigatinib

De Rimini Ml, Marco Tucci, Méher Ben Abdelghani, Nadim Farés et al.
Liver International
Cholangiocarcinoma and Gallbladder Cancer Studies
article

Prognostic Impact of Concomitant Genomic Alterations in FGFR2 ‐Positive Cholangiocarcinoma Treated With Pemigatinib

De Rimini Ml, Marco Tucci, Méher Ben Abdelghani, Nadim Farés, Mario Mandalà, Riccardo Giampieri, David Malka, Rossana Berardi, Matthieu Sarabi, Rodolphe Paulon, Sandrine Hiret, Alessandro Parisi, Monica Niger, Caterina Vivaldi, Blandine Delaunay, Eric Assénat, Anthony Turpin, Andrea Palloni, David Tougeron, Pascal Artru, Ludovic Evesque, Elena Mori, Anna Diana, Pierre Combe, Julien Edeline, Astrid Lièvre, Maria Bensi, Marion Stacoffe, Chiara Alessandra Cella, Giada Pinterpe, Rita Balsano, Mohamed Bouattour, Carolina Liguori, Antoine Hollebecque, Andrea Casadei‐Gardini, Matthieu Delaye, Silvio Ken Garattini, Camille Hervé, A Vienne, Raffaella Longarini, Jean Frédéric Blanc, Gaël Roth, Massimiliano Salati, Adelaide Mazzocca, Vincent Bourgeois, Rosine Guimbaud
article en

Abstract

BACKGROUND & AIMS: Anti-FGFR therapies changed the treatment landscape for patients with previously treated, advanced, or metastatic cholangiocarcinoma (CCA) harbouring FGFR2 fusions/rearrangements. However, primary resistance to FGFR inhibitors remains a key challenge. In the present real-world study, we aimed to evaluate the prognostic impact of concomitant GAs in patients with FGFR2-positive CCA treated with pemigatinib. METHODS: This study included PEMIREAL-PEMIBIL patients treated with pemigatinib in second or later lines. Only patients who underwent extensive DNA- and/or RNA-based next-generation sequencing (NGS) analysis were considered. Primary endpoint was progression-free survival (PFS), with overall response rate, disease control rate and overall survival (OS) as secondary endpoint. OS and PFS were calculated by Kaplan-Meier and log-rank test. Multivariate analysis used cox-regression model. Level of statistical significance p was 0.05. RESULTS: Of 72 patients of PEMIREAL-PEMIBIL, 63 patients had evaluable NGS data, with concomitant GAs identified in 28 patients (44.4%). The most frequently observed concomitant GAs involved BAP1 (7/63, 11.1%), CDKN2A (7/63, 11.1%), TP53 (6/63, 9.5%), CDKN2B (5/63, 7.9%), PTEN (3/63, 4.7%) and IDH1 (1/63, 1.5%). A significantly shorter PFS was observed in patients with CDKN2A mutations compared to CDKN2A wild-type tumours (4.79 vs. 8.66 months, p = 0.0011, HR: 3.48 95% CI: 0.91-13.24), and similarly in patients with BAP1 mutations compared to BAP1 wild-type tumours (5.97 vs. 8.52 months, p = 0.025, HR:2.55 95% CI: 0.72-9.00). No significant differences in OS were observed. CONCLUSIONS: Our results support the negative prognostic role of BAP1 and CDKN2A GAs on PFS in patients with locally advanced or metastatic CCA with FGFR2 gene fusion/rearrangement treated with pemigatinib in a real-world setting.

Liver InternationalVol. 46(8)
Università Cattolica del Sacro Cuore (IT), University of Pisa (IT), University of Modena and Reggio Emilia (IT), Marche Polytechnic University (IT), University of Udine (IT), Centre National de la Recherche Scientifique (FR), Humanitas University (IT), Vita-Salute San Raffaele University (IT), Inserm (FR), University of Perugia (IT), Hôpital Beaujon (FR), Centre Hospitalier Universitaire de Grenoble (FR), Institut Gustave Roussy (FR), Agostino Gemelli University Polyclinic (IT), Centre Hospitalier Universitaire de Toulouse (FR), Université de Poitiers (FR), Clinique des Cèdres (FR), Centre Hospitalier Universitaire de La Réunion (RE), Institut de Cancérologie Strasbourg (FR), Azienda Unita' Sanitaria Locale Di Modena (IT), Institute Mutualiste Montsouris (FR), Centre Hospitalier Universitaire de Tours (FR), Hôpital Bretonneau (FR), Centre Léon Bérard (FR), Institut de Cancérologie de l'Ouest (FR), Azienda Ospedaliera San Gerardo (IT), Centre Eugène Marquis (FR), Groupe Hospitalier Mutualiste de Grenoble (FR), Azienda USL di Bologna (IT), Hôpital Cardiologique du Haut-Lévêque (FR), Pôle Léonard de Vinci (FR), Hôpital Rangueil (FR), Hôpital Pontchaillou (FR), Hôpital Privé Jean Mermo (FR), Peuplements végétaux et bioagresseurs en milieu tropical (RE), Institut de Recherche en Cancérologie de Montpellier (FR), Ospedale D. Cotugno (IT), Grenoble Institute of Neurosciences (FR), Centre Antoine Lacassagne (FR), Université d'été de Boulogne-sur-Mer (FR), Hôpital Claude Huriez (FR), Fondazione IRCCS Istituto Nazionale dei Tumori (IT), IRCCS Humanitas Research Hospital (IT), Hospital of Prato (IT), University of Bari Aldo Moro (IT), European Institute of Oncology (IT), Institut Curie (FR), Université Grenoble Alpes (FR)
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