Background
Phase III double-blind RCT, N=226 (randomized 2:1; sorafenib n=150, placebo n=76) from 23 centres in China, South Korea, and Taiwan. Patients with advanced (unresectable or metastatic) HCC, no prior systemic therapy, Child-Pugh class A. Chronic hepatitis B was the predominant aetiology (~70%), reflecting Asia-Pacific epidemiology. Enrolled Sept 2005–Jan 2007.
Interventions and follow up
Arm A: Sorafenib 400mg orally twice daily in 6-week cycles
Arm B: Placebo twice daily in 6-week cycles
Primary endpoint: No predefined primary endpoint; assessed OS, TTP, TTSP, DCR, and safety
Median follow up: Not reported separately
Arm B: Placebo twice daily in 6-week cycles
Primary endpoint: No predefined primary endpoint; assessed OS, TTP, TTSP, DCR, and safety
Median follow up: Not reported separately
Results
OS: 6.5 vs 4.2mo, HR 0.68 (95% CI 0.50–0.93), P=.014
TTP: 2.8 vs 1.4mo, HR 0.57 (95% CI 0.42–0.79), P=.0005
DCR: 35.3% vs 15.8%
TTP: 2.8 vs 1.4mo, HR 0.57 (95% CI 0.42–0.79), P=.0005
DCR: 35.3% vs 15.8%
Adverse events
Dermatologic/GI: Grade 3–4 drug-related hand-foot skin reaction 10.7% (sorafenib) vs 0; diarrhoea 6.0% vs 0; HFSR led to dose reduction in 11.4%.
Constitutional: Grade 3–4 fatigue 3.4% vs 0; discontinuation for AEs was rare.
Constitutional: Grade 3–4 fatigue 3.4% vs 0; discontinuation for AEs was rare.
Conclusions
Sorafenib demonstrated a significant survival benefit versus placebo in Asian HCC patients, confirming efficacy in a population predominantly with HBV-related disease and poorer baseline prognosis (mOS 6.5 months vs 10.7 months in SHARP). The trial extended the evidence base for sorafenib globally and supported its worldwide regulatory approval.
Key Limitations
No predefined primary endpoint, making formal statistical hierarchy difficult to interpret. OS was shorter than in SHARP (6.5 vs 10.7 months for sorafenib), reflecting worse baseline prognosis in the Asia-Pacific population (more HBV, more extrahepatic spread at enrollment). No biomarker selection. The 2:1 randomisation was pragmatic but reduced power for the placebo arm. The absolute OS gain of 2.3 months was clinically modest.
Clinical Context
Together with SHARP, this trial established sorafenib as the global first-line standard for advanced HCC for over a decade (2008–2020), until IMbrave150 demonstrated superiority of atezolizumab+bevacizumab. Historically important for confirming efficacy in HBV-dominant populations and supporting regulatory approval by Asian agencies (NMPA, KFDA). The distinct prognosis of Asian HCC patients (shorter OS) has since informed global trial design.