Multicentre randomised phase II trial of gemcitabine+platinum, with or without trastuzumab, in advanced or metastatic urothelial carcinoma overexpressing Her2
(2015) European Journal of Cancer — Vol. 51, n° 1, p. 45-54 (2015)
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- 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.
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Oudard, S., Culine, S., Vano, Y., Goldwasser, F., Théodore, C., Nguyen, T., Voog, E., Banu, E., Vieillefond, A., Priou, F., Deplanque, G., Gravis, G., Ravaud, A., Vannetzel, J. M., Machiels, J.-P., Muracciole, X., Pichon, M.-F., Bay, J.-O., Elaidi, R., et al. (2015). Multicentre randomised phase II trial of gemcitabine+platinum, with or without trastuzumab, in advanced or metastatic urothelial carcinoma overexpressing Her2. European Journal of Cancer, 51(1), 45-54. https://doi.org/10.1016/j.ejca.2014.10.009 (Original work published 2015)