Phase 2 trial comparing sorafenib, pravastatin, their combination or supportive care in HCC with Child–Pugh B cirrhosis

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). Graphic abstract