Background
Multicenter, double-blind, placebo-controlled phase 3 trial in 602 patients with advanced hepatocellular carcinoma and Child-Pugh A liver function, randomized 1:1 to sorafenib or placebo.
Interventions and follow up
Arm A: Sorafenib 400 mg PO BID
Arm B: Placebo
Primary endpoint: OS and time to symptomatic progression
mFollow up: NR
Arm B: Placebo
Primary endpoint: OS and time to symptomatic progression
mFollow up: NR
Results
OS: 10.7mo vs 7.9mo; HR 0.69, 95% CI 0.55-0.87; P<.001
Time to symptomatic progression: 4.1mo vs 4.9mo; HR 1.08, 95% CI 0.88-1.31; P=.77
Time to radiologic progression: 5.5mo vs 2.8mo; HR 0.58, 95% CI 0.45-0.74; P<.001
Time to symptomatic progression: 4.1mo vs 4.9mo; HR 1.08, 95% CI 0.88-1.31; P=.77
Time to radiologic progression: 5.5mo vs 2.8mo; HR 0.58, 95% CI 0.45-0.74; P<.001
Adverse events
Overall: Any-grade events 80% vs 52% (Arm A vs B)
Dermatologic: Hand-foot skin reaction 29% vs 3%; alopecia 14% vs 2%; rash 17% vs 11% (Arm A vs B)
GI/constitutional: Diarrhea 47% vs 13%; anorexia 14% vs 4%; fatigue 26% vs 19% (Arm A vs B)
Dermatologic: Hand-foot skin reaction 29% vs 3%; alopecia 14% vs 2%; rash 17% vs 11% (Arm A vs B)
GI/constitutional: Diarrhea 47% vs 13%; anorexia 14% vs 4%; fatigue 26% vs 19% (Arm A vs B)
Conclusions
Sorafenib improved median overall survival and time to radiologic progression versus placebo in advanced hepatocellular carcinoma, the first systemic therapy to do so.
Key Limitations
Predominantly hepatitis C / alcohol-related etiology in a Western population; limited to Child-Pugh A; modest absolute OS gain; no benefit in time to symptomatic progression.
Clinical Context
SHARP led to FDA and EMA approval of sorafenib for unresectable HCC (2007), the standard first-line agent for a decade. It has since been displaced by atezolizumab/bevacizumab and remains a comparator and option for patients with contraindications to immunotherapy per ASCO/ESMO.