Multicentre randomised phase II trial of gemcitabine + platinum, with or without trastuzumab, in advanced or metastatic urothelial carcinoma overexpressing Her2. Issue 1 (January 2015)

• Record Type: Journal Article
• Authors: Oudard, Stéphane; Culine, Stéphane; Vano, Yann; Goldwasser, François; Théodore, Christine; Nguyen, Thierry; Voog, Eric; Banu, Eugeniu; Vieillefond, Annick; Priou, Franck; Deplanque, Gaël; Gravis, Gwenaëlle; Ravaud, Alain; Vannetzel, Jean Michel; Machiels, Jean-Pascal; Muracciole, Xavier; Pichon, Marie-France; Bay, Jacques-Olivier; Elaidi, Reza; Teghom, Corine; Radvanyi, François; Beuzeboc, Philippe
• Is Part Of: European journal of cancer. Volume 51:Issue 1(2015:Jan.)
• Page Start: 45
• Page End: 54
• Publication Date: 2015-01
• Subjects: Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2014.10.009
• Languages: English
• ISSNs: 0959-8049

Abstract

<abstract xml:lang="en" abstract-type="author" id="ab005"> <title id="st095">Abstract</title> <sec> <title id="st100">Aim</title> <p id="sp0005">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.</p> </sec> <sec> <title id="st105">Methods</title> <p id="sp0010">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 1000 mg/m<sup>2</sup> (days 1 and 8) plus either cisplatin (70 mg/m<sup>2</sup>) or carboplatin (AUC = 5) (day 1 every 3 weeks) or Arm B: added trastuzumab (8 mg/kg loading dose, then 6 mg/kg every 21 days until progression). The primary end-point was progression-free survival (PFS).</p> </sec> <sec> <title id="st110">Results</title> <p id="sp0015">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, <italic>p</italic> = 0.689), objective response rate (65.5% versus 53.2%, <italic>p</italic> = 0.39), and median overall survival (15.7 versus 14.1 months, respectively, <italic>p</italic> = 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.</p> </sec> <sec> <title id="st115">Conclusion</title> <p id="sp0020">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.</p> </sec> </abstract>