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Eur J Cancer. 2015 Jan;51(1):45-54. doi: 10.1016/j.ejca.2014.10.009. Epub 2014 Nov 15.

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

Author information

1
Department of Medical Oncology, Georges Pompidou Hospital, University Paris Descartes, Paris, France. Electronic address: stephane.oudard@egp.aphp.fr.
2
Department of Medical Oncology, Saint Louis Hospital, Paris, France.
3
Department of Medical Oncology, Georges Pompidou Hospital, University Paris Descartes, Paris, France.
4
Department of Medical Oncology, Cochin Hospital, Paris, France.
5
Department of Medical Oncology, Foch Hospital, Suresnes, France.
6
Department of Medical Oncology, Besançon University Hospital, Besançon, France.
7
Department of Medical Oncology, Victor Hugo Clinic, Le Mans, France.
8
Department of Oncology-Hematology, La Roche-Sur-Yon Hospital, La Roche-Sur-Yon, France.
9
Department of Medical Oncology, Saint Joseph Foundation, Paris, France.
10
Department of Medical Oncology, Paoli Calmettes Institute, Marseille, France.
11
Department of Medical Oncology, Bordeaux University Hospital, Bordeaux, France.
12
Department of Oncology, Clinique Hartman, Neuilly-sur-Seine, France.
13
Department of Medical Oncology, Saint Luc University Clinics, Catholic University of Leuven (IREC/MIRO, pole ONCO), Brussels, Belgium.
14
Department of Medical Oncology, La Timone Hospital, Marseille, France.
15
Oncobiology Laboratory, René Huguenin Center, St Cloud, France.
16
Department of Oncology, Saint Perrin Hospital, Clermont Ferrand, France.
17
ARTIC Group (Association de Recherche sur les Thérapeutiques innovantes en Cancérologie), France.
18
Molecular Oncology, Curie Institute, UMR 144, CNRS, Paris, France.
19
Department of Medical Oncology, Curie Institute, Paris, France.

Abstract

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01828736.

KEYWORDS:

Advanced urothelial carcinoma; Gemcitabine; Her2 overexpression; Platinum salts; Trastuzumab

PMID:
25459391
DOI:
10.1016/j.ejca.2014.10.009
[Indexed for MEDLINE]

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