Multicentre randomised phase II trial of gemcitabine+platinum, with or without trastuzumab, in advanced or metastatic urothelial carcinoma overexpressing Her2.

Autor: Oudard S; Department of Medical Oncology, Georges Pompidou Hospital, University Paris Descartes, Paris, France. Electronic address: stephane.oudard@egp.aphp.fr., Culine S; Department of Medical Oncology, Saint Louis Hospital, Paris, France., Vano Y; Department of Medical Oncology, Georges Pompidou Hospital, University Paris Descartes, Paris, France., Goldwasser F; Department of Medical Oncology, Cochin Hospital, Paris, France., Théodore C; Department of Medical Oncology, Foch Hospital, Suresnes, France., Nguyen T; Department of Medical Oncology, Besançon University Hospital, Besançon, France., Voog E; Department of Medical Oncology, Victor Hugo Clinic, Le Mans, France., Banu E; Department of Medical Oncology, Georges Pompidou Hospital, University Paris Descartes, Paris, France., Vieillefond A; Department of Medical Oncology, Cochin Hospital, Paris, France., Priou F; Department of Oncology-Hematology, La Roche-Sur-Yon Hospital, La Roche-Sur-Yon, France., Deplanque G; Department of Medical Oncology, Saint Joseph Foundation, Paris, France., Gravis G; Department of Medical Oncology, Paoli Calmettes Institute, Marseille, France., Ravaud A; Department of Medical Oncology, Bordeaux University Hospital, Bordeaux, France., Vannetzel JM; Department of Oncology, Clinique Hartman, Neuilly-sur-Seine, France., Machiels JP; Department of Medical Oncology, Saint Luc University Clinics, Catholic University of Leuven (IREC/MIRO, pole ONCO), Brussels, Belgium., Muracciole X; Department of Medical Oncology, La Timone Hospital, Marseille, France., Pichon MF; Oncobiology Laboratory, René Huguenin Center, St Cloud, France., Bay JO; Department of Oncology, Saint Perrin Hospital, Clermont Ferrand, France., Elaidi R; ARTIC Group (Association de Recherche sur les Thérapeutiques innovantes en Cancérologie), France., Teghom C; ARTIC Group (Association de Recherche sur les Thérapeutiques innovantes en Cancérologie), France., Radvanyi F; Molecular Oncology, Curie Institute, UMR 144, CNRS, Paris, France., Beuzeboc P; Department of Medical Oncology, Curie Institute, Paris, France.
Jazyk: angličtina
Zdroj: European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2015 Jan; Vol. 51 (1), pp. 45-54. Date of Electronic Publication: 2014 Nov 15.
DOI: 10.1016/j.ejca.2014.10.009
Abstrakt: Aim: To investigate the efficacy and safety of gemcitabine and platinum salt, with or without trastuzumab, in patients with locally advanced or metastatic urothelial carcinoma overexpressing Her2.
Methods: The main eligibility criterion was Her2 overexpression on immunohistochemistry (IHC 2+ or 3+) of primary tumour tissue confirmed by fluorescence in situ hybridisation (FISH). Patients were randomised to Arm A: gemcitabine 1000mg/m(2) (days 1 and 8) plus either cisplatin (70mg/m(2)) or carboplatin (AUC=5) (day 1 every 3 weeks) or Arm B: added trastuzumab (8mg/kg loading dose, then 6 mg/kg every 21 days until progression). The primary end-point was progression-free survival (PFS).
Results: Among 563 screened patients, 75 (13.3%) were Her2 positive (IHC 2+/3+ and FISH+) and 61 met all eligibility criteria (median age, 64 years; 54/61 males; 50/61 baseline ECOG-PS 0-1; 11 locally advanced and 50 metastatic). There was no significant difference between Arms A and B in median PFS (10.2 versus 8.2 months, respectively, p=0.689), objective response rate (65.5% versus 53.2%, p=0.39), and median overall survival (15.7 versus 14.1 months, respectively, p=0.684). In an exploratory analysis, trastuzumab-treated patients receiving cisplatin rather than carboplatin-based chemotherapy fared better (PFS: 10.6 versus 8.0; OS: 33.1 versus 9.5 months). Myelosuppression was the main grade 3/4 toxicity. A case of grade 3 cardiotoxicity and one death from febrile neutropenia occurred in arm B.
Conclusion: The unexpectedly low incidence of Her2 overexpression precluded the detection of a significant difference in efficacy on addition of trastuzumab to platinum-based chemotherapy with gemcitabine. However, the satisfactory tolerance of the combination warrants further studies, especially of the cisplatin-based combination, in well-defined patient subsets.
(Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: