Pravastatin combination with sorafenib does not improve survival in advanced hepatocellular carcinoma

• Published in: Journal of hepatology Vol. 71; no. 3; pp. 516 - 522
• Main Authors: Jouve, Jean-Louis, Lecomte, Thierry, Bouché, Olivier, Barbier, Emilie, Khemissa Akouz, Faiza, Riachi, Ghassan, Nguyen Khac, Eric, Ollivier-Hourmand, Isabelle, Debette-Gratien, Maryline, Faroux, Roger, Villing, Anne-Laure, Vergniol, Julien, Ramee, Jean-François, Bronowicki, Jean-Pierre, Seitz, Jean-François, Legoux, Jean-Louis, Denis, Jacques, Manfredi, Sylvain, Phelip, Jean-Marc
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-09-2019; Elsevier Science Ltd
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - mortality; Diarrhea; Diarrhea - chemically induced; Female; Follow-Up Studies; HCC; Hepatocellular carcinoma; Humans; Kaplan-Meier Estimate; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - mortality; Male; Medical prognosis; Middle Aged; Multivariate analysis; Nausea; Patients; Population studies; Pravastatin; Pravastatin - adverse effects; Pravastatin - therapeutic use; Prognosis; Progression-Free Survival; Quality of Life; RCT; Sorafenib - adverse effects; Sorafenib - therapeutic use; Statins; Survival; Systemic therapy; Toxicity; Tyrosine kinase inhibitors; Vomiting; Systemic therapy; Liver cancer; HCC; RCT; Tyrosine kinase inhibitors; Statins
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2019.04.021

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•Phase III, multicenter study, comparing sorafenib + pravastin to sorafenib alone in Child-Pugh A patients with HCC.•The sorafenib-pravastatin combination did not improve overall survival in our study population.•Significant prognostic factors for overall survival were CLIP score, performance status, and QoL scores.•In multivariate analysis, only CLIP score was a prognostic factor for overall survival.•The anticancer effect of statins may be more evident in the adjuvant setting, or in the early stages of carcinogenesis.
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.