Sorafenib + Pravastatin

The combination of sorafenib and pravastatin has been studied in clinical trials for advanced hepatocellular carcinoma (HCC). This combination therapy pairs sorafenib, a tyrosine kinase inhibitor that is the standard of care for advanced HCC, with pravastatin, a statin medication that has demonstrated anti-tumor activity in preclinical and clinical studies. ## Clinical Evidence Two key clinical trials have evaluated this combination: 1. **PRODIGE-11 Trial**: This was a randomized controlled trial that compared sorafenib-pravastatin combination versus sorafenib alone in patients with advanced HCC. The study included 323 Child-Pugh A patients with advanced HCC who were naive to systemic treatment. After a median follow-up of 35 months, the trial found no difference in median overall survival (OS) between the treatment arms (10.7 months for combination vs. 10.5 months for sorafenib alone). 2. **Phase II Multicentric Randomized Trial**: This double-blind placebo-controlled study (NCT01418729) investigated the efficacy and safety of sorafenib + pravastatin combination. While median OS did not differ significantly between groups (12.4 months for the combination vs. 11.6 months for the control group), the radiological time to progression (TTP) was notably higher in patients treated with sorafenib + pravastatin than in the control group (9.9 months vs. 3.2 months). ## Safety Profile The combination of sorafenib + pravastatin was found to be safe and well-tolerated in clinical studies. The main toxicity reported was diarrhea (severe in 11% of patients in the combination arm vs. 8.9% in the sorafenib-only arm in the PRODIGE-11 trial), while severe nausea-vomiting was rare, and no toxicity-related deaths were reported. ## Prognostic Factors Several prognostic factors were identified in these studies: * The presence of portal vein thrombosis was associated with worse overall survival * Vascular invasion was associated with decreased overall survival * The absence of dermatological events was associated with lower overall survival Despite showing some promise in extending time to progression, the addition of pravastatin to sorafenib did not improve overall survival in patients with advanced HCC compared to sorafenib alone.

Other names

Sorafenib-Pravastatin combination