Llovet et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378-390. PMID 18650514

One-paragraph summary

SHARP randomized patients with advanced HCC and preserved liver function to sorafenib or placebo. Median overall survival was 10.7 versus 7.9 months (HR 0.69), establishing the first systemic treatment with a survival benefit in HCC.

Key findings

• Survival benefit occurred without a high radiographic response rate.
• Toxicity included hand-foot skin reaction and diarrhea.
• The trial made Child-Pugh A, performance-preserved disease the evidence template for later systemic registration trials.

Limitations

• Predates modern immunotherapy, viral cure, and MASLD epidemiology.
• Does not answer treatment in Child-Pugh B/C.
• Placebo comparison cannot rank sorafenib against later active regimens.

Why it matters

SHARP ended decades of negative systemic trials and supplied the common comparator for the next generation of phase 3 studies.

Cited by wiki pages

• overview
• systemic therapy
• clinical trials landscape