Stéphane Oudard1, Stéphane Culine2, Yann Vano3, François Goldwasser4, Christine Théodore5, Thierry Nguyen6, Eric Voog7, Eugeniu Banu3, Annick Vieillefond4, Franck Priou8, Gaël Deplanque9, Gwenaëlle Gravis10, Alain Ravaud11, Jean Michel Vannetzel12, Jean-Pascal Machiels13, Xavier Muracciole14, Marie-France Pichon15, Jacques-Olivier Bay16, Reza Elaidi17, Corine Teghom17, François Radvanyi18, Philippe Beuzeboc19. 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. Crown
RCT Entities:
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. Crown
Authors: Francesco Soria; Marco Moschini; Andrea Haitel; Gregory J Wirth; Jose A Karam; Christopher G Wood; Morgan Rouprêt; Vitaly Margulis; Pierre I Karakiewicz; Alberto Briganti; Jay D Raman; Solene-Florence Kammerer-Jacquet; Romain Mathieu; Karim Bensalah; Yair Lotan; Mehmet Özsoy; Mesut Remzi; Kilian M Gust; Shahrokh F Shariat Journal: World J Urol Date: 2016-06-07 Impact factor: 4.226
Authors: Neeraj Agarwal; Sumanta K Pal; Andrew W Hahn; Roberto H Nussenzveig; Gregory R Pond; Sumati V Gupta; Jue Wang; Mehmet A Bilen; Gurudatta Naik; Pooja Ghatalia; Christopher J Hoimes; Dharmesh Gopalakrishnan; Pedro C Barata; Alexandra Drakaki; Bishoy M Faltas; Lesli A Kiedrowski; Richard B Lanman; Rebecca J Nagy; Nicholas J Vogelzang; Kenneth M Boucher; Ulka N Vaishampayan; Guru Sonpavde; Petros Grivas Journal: Cancer Date: 2018-03-08 Impact factor: 6.860