Pravastatin combination with sorafenib does not improve survival in advanced hepatocellular carcinoma.
Adult
Aged
Aged, 80 and over
Antineoplastic Agents
/ adverse effects
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Carcinoma, Hepatocellular
/ drug therapy
Diarrhea
/ chemically induced
Female
Follow-Up Studies
Humans
Kaplan-Meier Estimate
Liver Neoplasms
/ drug therapy
Male
Middle Aged
Pravastatin
/ adverse effects
Prognosis
Progression-Free Survival
Quality of Life
Sorafenib
/ adverse effects
HCC
Liver cancer
RCT
Statins
Systemic therapy
Tyrosine kinase inhibitors
Journal
Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
30
10
2018
revised:
23
04
2019
accepted:
30
04
2019
pubmed:
28
5
2019
medline:
15
12
2020
entrez:
25
5
2019
Statut:
ppublish
Résumé
Sorafenib is the standard of care for advanced hepatocellular carcinoma (HCC). Combining sorafenib with another treatment, to improve overall survival (OS) within an acceptable safety profile, might be the next step forward in the management of patients with advanced HCC. We aimed to assess whether a combination of sorafenib and a statin improved survival in patients with HCC. The objective of the PRODIGE-11 trial was to compare the respective clinical outcomes of the sorafenib-pravastatin combination (arm A) versus sorafenib alone (arm B) in patients with advanced HCC. Child-Pugh A patients with advanced HCC who were naive to systemic treatment (n = 323) were randomly assigned to sorafenib-pravastatin combination (n = 162) or sorafenib alone (n = 161). The primary endpoint was OS; secondary endpoints were progression-free survival, time to tumor progression, time to treatment failure, safety, and quality of life. After randomization, 312 patients received at least 1 dose of study treatment. After a median follow-up of 35 months, 269 patients died (arm A: 135; arm B: 134) with no difference in median OS between treatments arms (10.7 months vs. 10.5 months; hazard ratio = 1.00; p = 0.975); no difference was observed in secondary survival endpoints either. In the univariate analysis, the significant prognostic factors for OS were CLIP score, performance status, and quality of life scores. The multivariate analysis showed that the only prognostic factor for OS was the CLIP score. The main toxicity was diarrhea (which was severe in 11% of patients in arm A, and 8.9% in arm B), while severe nausea-vomiting was rare, and no toxicity-related deaths were reported. Adding pravastatin to sorafenib did not improve survival in patients with advanced HCC. Sorafenib has proven efficacy for the treatment of patients with advanced hepatocellular carcinoma. However, overall survival remains poor in these patients, so we were interested to see if the addition of a statin, pravastatin, improved outcomes in patients with advanced HCC. This randomized-controlled trial demonstrated that the sorafenib-pravastatin combination did not improve overall survival in this study population compared to sorafenib alone. Clinical trial number: NCT01075555.
Sections du résumé
BACKGROUND & AIMS
Sorafenib is the standard of care for advanced hepatocellular carcinoma (HCC). Combining sorafenib with another treatment, to improve overall survival (OS) within an acceptable safety profile, might be the next step forward in the management of patients with advanced HCC. We aimed to assess whether a combination of sorafenib and a statin improved survival in patients with HCC.
METHODS
The objective of the PRODIGE-11 trial was to compare the respective clinical outcomes of the sorafenib-pravastatin combination (arm A) versus sorafenib alone (arm B) in patients with advanced HCC. Child-Pugh A patients with advanced HCC who were naive to systemic treatment (n = 323) were randomly assigned to sorafenib-pravastatin combination (n = 162) or sorafenib alone (n = 161). The primary endpoint was OS; secondary endpoints were progression-free survival, time to tumor progression, time to treatment failure, safety, and quality of life.
RESULTS
After randomization, 312 patients received at least 1 dose of study treatment. After a median follow-up of 35 months, 269 patients died (arm A: 135; arm B: 134) with no difference in median OS between treatments arms (10.7 months vs. 10.5 months; hazard ratio = 1.00; p = 0.975); no difference was observed in secondary survival endpoints either. In the univariate analysis, the significant prognostic factors for OS were CLIP score, performance status, and quality of life scores. The multivariate analysis showed that the only prognostic factor for OS was the CLIP score. The main toxicity was diarrhea (which was severe in 11% of patients in arm A, and 8.9% in arm B), while severe nausea-vomiting was rare, and no toxicity-related deaths were reported.
CONCLUSION
Adding pravastatin to sorafenib did not improve survival in patients with advanced HCC.
LAY SUMMARY
Sorafenib has proven efficacy for the treatment of patients with advanced hepatocellular carcinoma. However, overall survival remains poor in these patients, so we were interested to see if the addition of a statin, pravastatin, improved outcomes in patients with advanced HCC. This randomized-controlled trial demonstrated that the sorafenib-pravastatin combination did not improve overall survival in this study population compared to sorafenib alone. Clinical trial number: NCT01075555.
Identifiants
pubmed: 31125576
pii: S0168-8278(19)30289-2
doi: 10.1016/j.jhep.2019.04.021
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Sorafenib
9ZOQ3TZI87
Pravastatin
KXO2KT9N0G
Banques de données
ClinicalTrials.gov
['NCT01075555']
Types de publication
Clinical Trial, Phase III
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
516-522Informations de copyright
Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.