Phase 2 trial comparing sorafenib, pravastatin, their combination or supportive care in HCC with Child-Pugh B cirrhosis.
Antineoplastic Agents
/ therapeutic use
Carcinoma, Hepatocellular
/ drug therapy
Drug Combinations
Humans
Liver Cirrhosis
/ complications
Liver Neoplasms
/ drug therapy
Niacinamide
/ therapeutic use
Phenylurea Compounds
/ therapeutic use
Pravastatin
/ therapeutic use
Prospective Studies
Sorafenib
/ therapeutic use
Treatment Outcome
ALBI
Child–Pugh
HCC
Liver functions
Randomized clinical trial
Sorafenib
Journal
Hepatology international
ISSN: 1936-0541
Titre abrégé: Hepatol Int
Pays: United States
ID NLM: 101304009
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
29
09
2020
accepted:
02
12
2020
pubmed:
10
1
2021
medline:
30
10
2021
entrez:
9
1
2021
Statut:
ppublish
Résumé
There is limited data regarding the role for systemic treatment in patients with Hepatocellular Carcinoma with Child-Pugh B cirrhosis. 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). 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. 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. The study was referenced in clinicaltrials.gov (NCT01357486).
Sections du résumé
BACKGROUND AND AIMS
OBJECTIVE
There is limited data regarding the role for systemic treatment in patients with Hepatocellular Carcinoma with Child-Pugh B cirrhosis.
METHODS
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
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
CONCLUSIONS
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
BACKGROUND
The study was referenced in clinicaltrials.gov (NCT01357486).
Identifiants
pubmed: 33420951
doi: 10.1007/s12072-020-10120-3
pii: 10.1007/s12072-020-10120-3
doi:
Substances chimiques
Antineoplastic Agents
0
Drug Combinations
0
Phenylurea Compounds
0
Niacinamide
25X51I8RD4
Sorafenib
9ZOQ3TZI87
Pravastatin
KXO2KT9N0G
Banques de données
ClinicalTrials.gov
['NCT01357486']
Types de publication
Clinical Trial, Phase II
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
93-104Subventions
Organisme : institut national du cancer
ID : PHRC10_04-02
Investigateurs
Evelyne Boucher
(E)
Marie Talarmin
(M)
Samuel Le Sourd
(S)
Julien Vergniol
(J)
Alice Gagnaire
(A)
Laurent Bedenne
(L)
Jean-Louis Jouve
(JL)
Patrick Hillon
(P)
Côme Lepage
(C)
Anne Minello
(A)
Hélène Barraud
(H)
Thierry Lecomte
(T)
Jean-Pierre Barbieux
(JP)
Patrice Wolff
(P)
Valérie Phoutthasang
(V)
Christine Belletier
(C)
Isabelle Archambeaud
(I)
Tamara Matysiak Budnik
(TM)
Matthieu Schnee
(M)
Muriel Duluc
(M)
Emmanuelle Norguet Monnereau
(EN)
Jaafar Bennouna
(J)
Sandrine Hiret
(S)
Michel Gatineau
(M)
Mohamed Ramdani
(M)
Yann Le Bricquir
(Y)
Nathalie Ganne-Carrie
(N)
Valérie Bourcier
(V)
Christophe Pilette
(C)
Barbara Dauvois
(B)
Mathieu Baconnier
(M)
Pierre Michel
(P)
Philippe Thevenet
(P)
Hélène Cosme-Gassmann
(H)
François Habersetzer
(F)
Camélia Coltescu
(C)
Mathieu Pauwels
(M)
Sophie Nahon Brissonneau
(SN)
Joëlle Egreteau
(J)
Jérôme Desrame
(J)
Dominique Auby
(D)
Patrick Texereau
(P)
Pierre-Luc Etienne
(PL)
Louis-Marie Dourthe
(LM)
Youssef Tazi
(Y)
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