786O - Multicenter randomized phase 2 trial of gemcitabine - platinum with or without trastuzumab (T) in advanced / metastatic urothelial carcinoma (a/mUC)...

Date 30 September 2012
Event ESMO Congress 2012
Session Genitourinary tumors, bladder and testicular cancer
Topics Cytotoxic agents
Urothelial Cancers
Therapy
Biological therapy
Presenter Stephane Oudard
Authors S. Oudard1, S. Culine2, A. Vieillefond3, F. Priou4, F. Goldwasser3, A. Ravaud5, G. Gravis6, G. Deplanque7, J. Machiels8, P. Beuzeboc9
  • 1Medical Oncology Service, Hopital Européen, FR-75015 - Paris/FR
  • 2Oncology, Hôpital Saint-Louis, 75010 - Paris/FR
  • 3Oncology, Cochin Hospital, 75014 - Paris/FR
  • 4Service D'onco-hématologie, Centre Hospitalier Les Oudairies, La Roche-sur-Yon/FR
  • 5Medical Oncology, Bordeaux University Hospital Saint André, 33075 - Bordeaux/FR
  • 6Medical Oncology, Paoli Calmettes, 13009 - Marseille/FR
  • 7Hopital St. Joseph, FR-75014 - Paris/FR
  • 8Medical Oncology, Cliniques Universitaires St. Luc, 01200 - Brussels/BE
  • 9Medical Oncology Unit, Curie Institute, 75005 - Paris/FR

 

Abstract

Background

a/mUC are associated with poor prognosis and HER2 overexpression is observed in around 10%. T combined with chemotherapy led to improvement of overall survival (OS) in metastatic breast and gastric cancers patients (pts). We investigated efficacy and safety of T combined with gemcitabine (G) and cis- (Ci) or carbo-platinum (Ca) in this population.

Methods

a/mUC pts were screened for HER2,(IHC: score 3+ or 2+ with positive FISH). Chemotherapy (CT)-naïve pts were randomized: Arm A (GCi-Ca) = G (1000 mg/m2 on D1 & 8) and Ci (70 mg/m2) or Ca (AUC 5 on D1 every 3 weeks for 6 cycles with creatinine clearance cut-off > 60 ml/min); Arm B (GCi-CaT)= Arm A + T (8 mg/kg charging dose then 6 mg/kg every cycle until progression). End-points: primary= PFS, secondary= OS, ORR and toxicity.

Results

Pts were screened from 2003 to 2008: 61 pts (59 HER2-3+ and 2 HER2-2 + /FISH+) were eligible, 32 (52%) and 29 (48%) were randomized in arms A and B, respectively. 52% and 48% received Ci and Ca respectively. Median age: 64 yr, sex-ratio = 54/7; local treatment: surgery = 59 (98%), radiotherapy = 13 (22%), neo/adjuvant CT = 18 (30%). Baseline: ECOG-PS 0-1 = 50 (82%), 2 = 11 (18%); primary disease site: bladder = 54 (89%); locally advanced: 11 (18%), metastatic: 50 (82%); visceral metastasis: 34 (57%). Median cycle number = 6 (range: 3-9). Grade 3/4 toxicities: neutropenia (72%, febrile = 3%), thrombocytopenia (43%), anaemia (38%) were comparable between 2 arms. Dyspnea was mainly observed in GCi-CaT (16.2% vs 3.4%). No toxic death occurred. Median PFS (months = m) was 10.2 [95%CI: 5.2–13.4] and 9.3 [95%CI: 6.5–15.7] (p = 0.7) in the GCi-Ca and GCi-CaT arms, respectively. ORR was 66% and 53% in the GCi-Ca and GCi-CaT arms, respectively. Median OS (m) was 15.7 [95%CI: 10.2–23.7] and 16.8 [95%CI: 6.7–31.2] in the GCi-Ca and GCi-CaT arms, respectively. Longest OS was observed in GCiT sub-group: 28 [95%CI: 12.4–50].

Conclusion

HER2 over-expression is rare in a/mUCs. No conclusion could be drawn on PFS due to lack of power. Dyspnea was more frequent in GCi-CaT arm. We hypothesize that trastuzumab could have a synergetic effect with cisplatinum leading to a longer OS.

Disclosure

S. Oudard: Advisory board or board of directors position to disclose: sanofi aventis, Bayer, Novartis, Roche, Pfizer Compensated relationship to disclose: Roche, Novartis Honoraria to disclose: Sanofi Anventis, Bayer, Novartis, Roche, Pfizer

F. Goldwasser: Advisory board: Bayer Novartis Roche Pfizer Amgen Frésénius Compensated consultant role: Novartis Roche Bayer Pfizer Amgen Honoraria: Roche Bayer Pfizer Novartis Research funding: Roche Amgen Bayer Pfizer Nutricia Other: AACR 2012 meeting: Bayer

J.P. Machiels: Uncompensated consultant role: Boerhinger Ingelheim; Research funding to disclose: Sanofi;

P. Beuzeboc: Compensated consultant role to disclose: Roche Honoraria to disclose: Roche.

All other authors have declared no conflicts of interest.