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 Anti-Cancer Agents & Biologic Therapy
Urothelial Cancers
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.