System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Ppublish

PubMed: 42494243 DOI: 10.1111/liv.70813

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

Liver Int 46(8):e70813

Authors: Carolina Liguori, Riccardo Giampieri, Blandine Delaunay, Giada Pinterpe, Adelaide Mazzocca, Antoine Hollebecque, Jean Frederic Blanc, Mohamed Bouattour, Eric Assenat, Meher Ben Abdelghani, Matthieu Sarabi, Monica Niger, Caterina Vivaldi, Mario Mandalà, Andrea Palloni, Maria Bensi, Silvio Ken Garattini, David Tougeron, Pierre Combe, Massimiliano Salati, Margherita Rimini, Andrea Casadei-Gardini, Chiara Alessandra Cella, Marco Tucci, Anna Diana, Elena Mori, Raffaella Longarini, Pascal Artru, Gael Roth, Ludovic Evesque, Agathe Vienne, Anthony Turpin, Sandrine Hiret, Vincent Bourgeois, Camille Herve, Rodolphe Paulon, Marion Stacoffe, David Malka, Matthieu Delaye, Julien Edeline, Astrid Lievre, Rosine Guimbaud, Rita Balsano, Nadim Fares, Rossana Berardi, Alessandro Parisi

Affiliations

  • Clinica Oncologica e Centro Regionale di Genetica Oncologica, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria delle Marche, Ancona, Italy.
  • Digestive Oncology Department, Centre Hospitalier Universitaire de Toulouse - Hopital Rangueil, Toulouse, France.
  • Département d'Innovation Thérapeutique et Essais précoces (DITEP), Gustave Roussy, Villejuif, Cedex, France.
  • Oncology Digestive Unit, Hôpital haut-Lévêque, CHU de Bordeaux, Bordeaux, France.
  • Liver Oncology and Therapeutic Innovation Functional Unit, Beaujon Hospital APHP, Clichy, France.
  • Medical Oncology, ICM - Institut du Cancer de Montpellier, Montpellier, Cedex, France.
  • Oncology Department, ICANS - Institut de Cancérologie Strasbourg Europe, Strasbourg, France.
  • GI Oncology Department, Medical Oncology, Centre Léon Bérard, Lyon, France.
  • GI Oncology Department, Hôpital privé Jean Mermoz, Lyon, France.
  • Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
  • Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
  • Unit of Medical Oncology, University of Perugia, Perugia, Italy.
  • Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
  • Oncologia Medica, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, Roma, Italy.
  • Università Cattolica del Sacro Cuore, Roma, Italy.
  • Department of Oncology, Academic Hospital of Udine ASUFC, Udine, UD, Italy.
  • Department of Gastroenterology and Hepatology, Poitiers University Hospital, Poitiers, France.
  • Medical Oncology, CORT37, Pôle Santé Léonard de Vinci, Chambray-lès-Tours, France.
  • Division of Oncology, Department of Oncology and Hematology, University Hospital Modena, Modena Cancer Centre, Modena, Italy.
  • Clinical and Experimental Medicine, University of Modena and Reggio Emilia, Modena, Italy.
  • Department of Oncology, Vita-Salute University San Raffaele, IRCCS San Raffaele Hospital, Milan, Italy.
  • Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO IRCCS, Milan, Italy.
  • Department of Interdisciplinary Medicine, Oncology Unit, University of Bari "Aldo Moro", Bari, Italy.
  • UOC Oncologia - Ospedale del Mare, Naples, Italy.
  • Department of Medical Oncology, New Hospital of Prato S. Stefano, Prato, Italy.
  • Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
  • Univ. Grenoble Alpes/Hepato-Gastroenterology and Digestive Oncology Department, CHU Grenoble Alpes/Institute for Advanced Biosciences, CNRS UMR 5309-INSERM U1209, Grenoble, France.
  • Medical Oncology Department, Centre Antoine-Lacassagne, Nice, France.
  • Oncology Department, CHU Sud Réunion, Saint Pierre, France.
  • Medical Oncology Department, Hospital Claude Huriez, Lille, France.
  • Oncology Department, ICO Institut de Cancerologie de l'Ouest René Gauducheau, Saint-Herblain, France.
  • Digestive Oncology, Hopital duchenne, Boulogne-sur-Mer, France.
  • Digestive Oncology, Groupe Hospitalier Mutualiste, Grenoble, France.
  • Medical Oncology, Clinique du Sidobre, Castres, France.
  • Medical Oncology, CHRU Hopitaux de Tours - Hopital Bretonneau, Tours, Cedex, France.
  • Medical Oncology, Institut Mutualiste Montsouris, Paris, France.
  • GI Oncology, Medical Oncology Department, Curie Institute, Paris, France.
  • Medical Oncology Department, Centre Eugene-Marquis, Rennes, France.
  • Department of Gastroenterology, CHU de Rennes - Hopital Pontchaillou, Rennes, Cedex, France.
  • Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
  • Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.

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.

MeSH

Genes, Liver, Therapeutics, Mutation, Prognosis, Cholangiocarcinoma