TRASTUZUMAB FOR BLADDER CANCER?

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.

Oudard S1, Culine S2, Vano Y3, Goldwasser F4, Théodore C5, Nguyen T6, Voog E7, Banu E3, Vieillefond A4, Priou F8, Deplanque G9, Gravis G10, Ravaud A11, Vannetzel JM12, Machiels JP13, Muracciole X14, Pichon MF15, Bay JO16, Elaidi R17, Teghom C17, Radvanyi F18, Beuzeboc P19.

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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 3weeks) or Arm B: added trastuzumab (8mg/kg loading dose, then 6mg/kg every 21days 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, 64years; 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 8.2months, respectively, p=0.689), objective response rate (65.5% versus 53.2%, p=0.39), and median overall survival (15.7 versus 14.1months, 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 9.5months). 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.