Jean-Frédéric Blanc1, Faiza Khemissa2, Jean-Pierre Bronowicki3, Carole Monterymard4, Jean-Marc Perarnau5, Vincent Bourgeois6, Stéphane Obled7, Meher Ben Abdelghani8, Isabelle Mabile-Archambeaud9, Roger Faroux10, Jean-François Seitz11, Christophe Locher12, Hélène Senellart13, Anne-Laure Villing14, Franck Audemar15, Charlotte Costentin16, Gaël Deplanque17, Sylvain Manfredi18, Julien Edeline19. 1. Hepatology, CHU Bordeaux, (HOPITAL SAINT-ANDRE-CHU), 1 Rue Jean Burguet, 33000, Bordeaux, France. jean-frederic.blanc@chu-bordeaux.fr. 2. CH Saint Jean, Perpignan, France. 3. CHU Nancy-Brabois, Vandoeuvre les Nancy, France. 4. FFCD, Dijon, France. 5. CHU Tours Hôpital Trousseau, Tours, France. 6. Hôpital Duchenne, Boulogne-Sur-Mer, France. 7. CHU Carémeau, Nîmes, France. 8. Centre Paul Strauss, Strasbourg, France. 9. CHU Hôtel Dieu, Nantes, France. 10. CHD Vendée, La Roche-Sur-Yon, France. 11. CHU la TIMONE, Marseille, France. 12. Centre Hospitalier de Meaux, Meaux, France. 13. ICO Centre René Gauducheau, Saint-Herblain, France. 14. Centre Hospitalier Auxerre, Auxerre, France. 15. CH de la Côte Basque, Bayonne, France. 16. AP-HP Hôpital Henri Mondor, Créteil, France. 17. Groupe Hospitalier Saint Joseph, Paris, France. 18. Faculté de Médecine, INSERM U1231, Université de Bourgogne, Franche-Comté, Dijon, France. 19. Centre Eugène Marquis, Rennes, France.
Abstract
BACKGROUND AND AIMS: There is limited data regarding the role for systemic treatment in patients with Hepatocellular Carcinoma with Child-Pugh B cirrhosis. METHODS: PRODIGE 21 was a multicentric prospective non-comparative randomized trial. Patients were randomized to receive sorafenib (Arm A), pravastatin (Arm B), sorafenib-pravastatin (Arm C) combination, or best supportive care (Arm D). Primary endpoint was time to progression (TTP), secondary endpoints included safety and overall survival (OS). RESULTS:160 patients were randomized and 157 patients were included in the final analysis. 86% of patients were BCLC C and 55% had macrovascular invasion. The safety profiles of the drugs were as expected. Median TTP was 3.5, 2.8, 2.0 and 2.2 months in arms A, B, C and D, respectively, but analysis was limited by the number of patients deceased without radiological progression (59%). Median OS was similar between the four arms: 3.8 [95% CI: 2.4-6.5], 3.1 [95% CI: 1.9-4.3], 4.0 [95% CI: 3.2-5.5] and 3.5 months [95% CI: 2.2-5.4] in arms A, B, C and D, respectively. Median OS was 4.0 months [95% CI: 3.3-5.5] for patients treated with sorafenib, vs 2.9 months [95% CI: 2.2-3.9] for patients not treated with sorafenib. In patients with ALBI grade 1/2, median OS was 6.1 months [95% CI: 3.8-8.3] in patients treated with sorafenib vs 3.1 months [95% CI: 1.9-4.8] for patients not treated with sorafenib. CONCLUSION: In the overall Child-Pugh B population, neither sorafenib nor pravastatin seemed to provide benefit. In the ALBI grade 1/2 sub-population, our trial suggests potential benefit of sorafenib. CLINICAL TRIAL REGISTRATION: The study was referenced in clinicaltrials.gov (NCT01357486).
RCT Entities:
BACKGROUND AND AIMS: There is limited data regarding the role for systemic treatment in patients with Hepatocellular Carcinoma with Child-Pugh B cirrhosis. METHODS: PRODIGE 21 was a multicentric prospective non-comparative randomized trial. Patients were randomized to receive sorafenib (Arm A), pravastatin (Arm B), sorafenib-pravastatin (Arm C) combination, or best supportive care (Arm D). Primary endpoint was time to progression (TTP), secondary endpoints included safety and overall survival (OS). RESULTS: 160 patients were randomized and 157 patients were included in the final analysis. 86% of patients were BCLC C and 55% had macrovascular invasion. The safety profiles of the drugs were as expected. Median TTP was 3.5, 2.8, 2.0 and 2.2 months in arms A, B, C and D, respectively, but analysis was limited by the number of patients deceased without radiological progression (59%). Median OS was similar between the four arms: 3.8 [95% CI: 2.4-6.5], 3.1 [95% CI: 1.9-4.3], 4.0 [95% CI: 3.2-5.5] and 3.5 months [95% CI: 2.2-5.4] in arms A, B, C and D, respectively. Median OS was 4.0 months [95% CI: 3.3-5.5] for patients treated with sorafenib, vs 2.9 months [95% CI: 2.2-3.9] for patients not treated with sorafenib. In patients with ALBI grade 1/2, median OS was 6.1 months [95% CI: 3.8-8.3] in patients treated with sorafenib vs 3.1 months [95% CI: 1.9-4.8] for patients not treated with sorafenib. CONCLUSION: In the overall Child-Pugh B population, neither sorafenib nor pravastatin seemed to provide benefit. In the ALBI grade 1/2 sub-population, our trial suggests potential benefit of sorafenib. CLINICAL TRIAL REGISTRATION: The study was referenced in clinicaltrials.gov (NCT01357486).
Authors: C Lersch; R Schmelz; J Erdmann; R Hollweck; E Schulte-Frohlinde; F Eckel; M Nader; V Schusdziarra Journal: Hepatogastroenterology Date: 2004 Jul-Aug
Authors: Enrica Rossini; Federico Biscetti; Maria Margherita Rando; Elisabetta Nardella; Andrea Leonardo Cecchini; Maria Anna Nicolazzi; Marcello Covino; Antonio Gasbarrini; Massimo Massetti; Andrea Flex Journal: Int J Mol Sci Date: 2022-08-18 Impact factor: 6.208