Boost: A phase 3 trial of sorafenib vs. best supportive care in first line treatment of hepatocellular carcinoma in patients with deteriorated liver function

Aim: Only patients with good liver function {[Child-Pugh (CP)] A class} were eligible for trials testing sorafenib as first-line treatment of hepatocellular carcinoma (HCC); nevertheless, the drug was authorized without restrictions based on liver function. Therefore, we planned to test sorafenib efficacy and safety in patients with HCC and deteriorated liver function (CP-B). Methods: This was an open-label, multicenter, randomized phase 3 trial. Patients with HCC, no previous systemic therapy, and CP-B score 7-9 were assigned 1:1 to best supportive care alone (control arm) or with standard dose sorafenib (experimental arm). Overall survival (OS) was the primary endpoint. To detect a 0.70 HR of death, with 80% power, and two-tailed α error 0.05, 234 events were required. The study closed prematurely because of slow accrual. Descriptive analyses are reported. Results: From 2012 to 2017, 13 Italian centers randomized 35 patients. In total, 28 deaths were recorded, 12 without and 16 with sorafenib; median OS was 4.9 (95%CI: 1.2-5.6) and 3.5 months (95%CI: 1.3-5.3), respectively. At least one severe adverse event was reported in 2/15 (13.3%) without and 9/17 (52.9%) patients with sorafenib. Conclusions: This trial failed its planned enrolment goal, showing the difficulty in performing clinical trials with drugs already registered with a label broader than what available evidence supports.