SHARP: trial | Bending the Curve: Trial by Trial

SHARP

Sorafenib in advanced hepatocellular carcinoma

Population

Patients with advanced hepatocellular carcinoma who had not received previous systemic treatment

Design

Multicentre, double-blind, placebo-controlled phase 3 trial; sorafenib 400 mg twice daily versus placebo. Primary outcomes were overall survival and time to symptomatic progression; time to radiologic progression and safety were secondary. The study was stopped at the second planned interim analysis, after 321 deaths.

Primary endpoint

OS, Time to symptomatic progression

Arms

Sorafenib (experimental): Sorafenib 400 mg twice daily
Placebo (control): Placebo

People

Llovet JM, SHARP Investigators Study Group

OSHR 0.69 (95% CI 0.55–0.87)Δ median OS+2.8 monthsΔ median Time to symptomatic progression−0.8 monthsΔ median Time to radiologic progression+2.7 months

Show the numbers

Results reported for SHARP
Endpoint	Analysis	Sorafenib	Placebo	Effect
OSRandomised patients as described in the abstract (analysis population not stated there)	interimLlovet 2008	median 10.7 months	median 7.9 months	HR 0.69 (95% CI 0.55–0.87)P<0.001Reported at the second planned interim analysis (321 deaths), at which the study was stopped.
Time to symptomatic progressionRandomised patients as described in the abstract (analysis population not stated there)	interimLlovet 2008	median 4.1 months	median 4.9 months	P=0.77Co-primary outcome; the abstract reports no significant difference between the groups.
Time to radiologic progressionRandomised patients as described in the abstract (analysis population not stated there)	interimLlovet 2008	median 5.5 months	median 2.8 months	P<0.001Secondary outcome.

Results reported for SHARP
Endpoint	Analysis	Sorafenib	Placebo	Effect
OSRandomised patients as described in the abstract (analysis population not stated there)	interimLlovet 2008	median 10.7 months	median 7.9 months	HR 0.69 (95% CI 0.55–0.87)P<0.001Reported at the second planned interim analysis (321 deaths), at which the study was stopped.
Time to symptomatic progressionRandomised patients as described in the abstract (analysis population not stated there)	interimLlovet 2008	median 4.1 months	median 4.9 months	P=0.77Co-primary outcome; the abstract reports no significant difference between the groups.
Time to radiologic progressionRandomised patients as described in the abstract (analysis population not stated there)	interimLlovet 2008	median 5.5 months	median 2.8 months	P<0.001Secondary outcome.

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
OS	0.69	0.55–0.87

Illustrative — modelled from reported values, not trial data. OS, interim.

Show curves

Sorafenib (experimental)
Placebo (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Sorafenib	Placebo
0	100.0%	100.0%
7	63.5%	54.1%
13	43.1%	32.0%
20	27.4%	17.3%
27	17.4%	9.4%

Illustrative — modelled from reported values, not trial data. Time to symptomatic progression, interim.

Show curves

Sorafenib (experimental)
Placebo (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Sorafenib	Placebo
0	100.0%	100.0%
3	60.2%	65.4%
6	36.3%	42.8%
9	21.8%	28.0%
12	13.2%	18.3%

Appears in

2007 Sorafenib: SHARP and Asia-Pacific trials in advanced HCC

Sources

Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378-90.
PubMed DOI