Marc Ychou1, Michel Rivoire2, Simon Thezenas3, Rosine Guimbaud4, Francois Ghiringhelli5, Anne Mercier-Blas6, Laurent Mineur7, Eric Francois8, Faiza Khemissa9, Marion Chauvenet10, Reza Kianmanesh11, Marianne Fonck12, Philippe Houyau13, Thomas Aparicio14, Marie-Pierre Galais15, Franck Audemar16, Eric Assenat17, Evelyne Lopez-Crapez18, Claire Jouffroy19, Antoine Adenis20, René Adam21, Olivier Bouché22. 1. Department of Digestive Oncology, Institut du Cancer de Montpellier, Montpellier, France. marc.ychou@icm.unicancer.fr. 2. Department of Surgical Oncology, Léon Bérard Cancer Center, Lyon, France. 3. Biometrics Unit, Institut du Cancer de Montpellier, Montpellier, France. 4. Department of Digestive Oncology - IUCT Rangueil-Larrey, CHU de Toulouse, Toulouse, France. 5. Department of Medical Oncology, Centre Georges François Leclerc, Dijon, France. 6. Department of Medical Oncology, Centre Hospitalier Privé de Saint-Grégoire, Saint-Grégoire, France. 7. Department of Digestive Oncology, Institut Sainte Catherine, Avignon, France. 8. Department of Medical Oncology, Centre Antoine Lacassagne, Nice, France. 9. Gastroenterology unit, Centre Hospitalier Saint-Jean, Perpignan, France. 10. Department of Hepato-gastroenterology and Digestive Oncology, Hôpital Lyon Sud, Lyon, France. 11. Department of Digestive and Endocrine Surgery, Hôpital Robert Debré, Reims, France. 12. Department of Digestive Oncology, Institut Bergonié, Bordeaux, France. 13. Department of Medical Oncology, Clinique Claude Bernard, Albi, France. 14. Department of Gastroenterology and Digestive Oncology, Hôpital Saint Louis, APHP, Paris, France. 15. Department of Medical Oncology, Centre François Baclesse, Caen, France. 16. Gastroenterology unit, Centre hospitalier Côte Basque, Bayonne, France. 17. Department of Digestive Oncology, CHU Saint Eloi, Montpellier, France. 18. Translational Research Unit, Institut du Cancer de Montpellier, Montpellier, France and IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Montpellier, France. 19. R&D Unicancer, Paris, France. 20. Department of Digestive Oncology, Institut du Cancer de Montpellier, Montpellier, France. 21. Hepatobiliary Centre, Paul Brousse Hospital, AP-HP, Villejuif, France. 22. Department of Hepatogastroenterology and Digestive Oncology, Hôpital Robert Debré, Reims, France.
Abstract
BACKGROUND: Colorectal cancer (CRC) patients have a better prognosis if metastases are resectable. Initially, unresectable liver-only metastases can be converted to resectable with chemotherapy plus a targeted therapy. We assessed which of chemotherapy doublet (2-CTx) or triplet (3-CTx), combined with targeted therapy by RAS status, would be better in this setting. METHODS: PRODIGE 14 was an open-label, multicenter, randomised Phase 2 trial. CRC patients with initially defined unresectable liver-only metastases received either, 2-CTx (FOLFOX or FOLFIRI) or 3-CTx (FOLFIRINOX), plus bevacizumab/cetuximab by RAS status. The primary endpoint was to increase the R0/R1 liver-resection rate from 50 to 70% with the 3-CTx. RESULTS: Patients (n = 256) were mainly men with an ECOG PS of 0, and a median age of 60 years. In total, 109 patients (42.6%) had RAS-mutated tumours. After a median follow-up of 45.6 months, the R0/R1 liver-resection rate was 56.9% (95% CI: 48-66) with the 3-CTx versus 48.4% (95% CI: 39-57) with the 2-CTx (P = 0.17). Median overall survival was 43.4 months with 3-CTx versus 40 months with 2-CTx. CONCLUSION: We failed to increase from 50 to 70% the R0/R1 liver-resection rate with the use of 3-CTx combined with bevacizumab or cetuximab by RAS status in CRC patients with initially unresectable liver metastases.
BACKGROUND: Colorectal cancer (CRC) patients have a better prognosis if metastases are resectable. Initially, unresectable liver-only metastases can be converted to resectable with chemotherapy plus a targeted therapy. We assessed which of chemotherapy doublet (2-CTx) or triplet (3-CTx), combined with targeted therapy by RAS status, would be better in this setting. METHODS: PRODIGE 14 was an open-label, multicenter, randomised Phase 2 trial. CRC patients with initially defined unresectable liver-only metastases received either, 2-CTx (FOLFOX or FOLFIRI) or 3-CTx (FOLFIRINOX), plus bevacizumab/cetuximab by RAS status. The primary endpoint was to increase the R0/R1 liver-resection rate from 50 to 70% with the 3-CTx. RESULTS: Patients (n = 256) were mainly men with an ECOG PS of 0, and a median age of 60 years. In total, 109 patients (42.6%) had RAS-mutated tumours. After a median follow-up of 45.6 months, the R0/R1 liver-resection rate was 56.9% (95% CI: 48-66) with the 3-CTx versus 48.4% (95% CI: 39-57) with the 2-CTx (P = 0.17). Median overall survival was 43.4 months with 3-CTx versus 40 months with 2-CTx. CONCLUSION: We failed to increase from 50 to 70% the R0/R1 liver-resection rate with the use of 3-CTx combined with bevacizumab or cetuximab by RAS status in CRC patients with initially unresectable liver metastases.
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Authors: Marc Ychou; Michel Rivoire; Simon Thezenas; François Quenet; Jean-Robert Delpero; Christine Rebischung; Christian Letoublon; Rosine Guimbaud; Eric Francois; Michel Ducreux; Françoise Desseigne; Jean-Michel Fabre; Eric Assenat Journal: Ann Surg Oncol Date: 2013-08-17 Impact factor: 5.344
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