There are no proven or approved second-line systemic treatment options for HCC. We evaluated regorafenib, an oral multikinase inhibitor, in patients with HCC who had disease progression on sorafenib.
Adults with BCLC stage B or C HCC who had radiological progression on sorafenib, Child-Pugh A liver function, and ECOG PS 0–1 were randomized 2:1 to regorafenib 160 mg/day or placebo on weeks 1–3 of each 4-week cycle until progression, death, or unacceptable toxicity. The primary endpoint was overall survival (OS). HRQoL was assessed by the FACT-Hep and EQ-5D questionnaires.
A total of 573 patients were randomized (regorafenib 379; placebo 194) and baseline characteristics were balanced. The regorafenib group had a 37% reduction in the risk of death (HR 0.63; 95%CI 0.50–0.79; p < 0.001); median OS (regorafenib vs placebo) was 10.6 vs 7.8 months. Regorafenib improved progression-free survival (HR 0.46; 95%CI 0.37–0.56; p < 0.001), time to progression (HR 0.44; 95%CI 0.36–0.55; p < 0.001), and the disease control rate (65.2% vs 36.1%; p < 0.001). Rates of grade ≥3 adverse events were 79.7% with regorafenib and 58.5% with placebo. Most common grade ≥3 adverse events occurring more frequently with regorafenib included hypertension (15.2% vs 4.7%), hand–foot skin reaction (12.6% vs 0.5%), fatigue (9.1% vs 4.7%), and diarrhea (3.2% vs 0%). The EQ-5D index, EQ-5D VAS, and FACT-G scores were similar in the treatment groups (Table). Although the FACT-Hep total score favored placebo, the difference did not meet the established minimally important threshold of 8–9 points.