Sorafenib (Nexavar) Improves Outcomes in Patients with Hepatocellular Carcinoma

Liver cancer is the third leading cause of cancer death worldwide. Chronic hepatitis C virus (HCV) infection is among the most common causes of hepatocellular carcinoma (HCC), and the incidence of this form of liver cancer is rising as people infected with HCV years or decades ago reach the later stages of disease.

Unfortunately, HCC is difficult to treat because it is often diagnosed late - although a recent study found that liver cancer screening can improve survival rates for individuals with chronic hepatitis B or C.

In a late-breaker presentations at the 43rd annual meeting of the European Association for the Study of the Liver (EASL 2008) last month in Milan, researchers discussed data from the SHARP study, which evaluated sorafenib (Nexavar) as a therapy for HCC. Sorafenib, which was already approved for primary kidney cancer, recently received U.S. Food and Drug Administration (FDA) approval for unresectable (not curable by surgery) HCC.

The SHARP (Sorafenib HCC Assessment Randomized Protocol) trial demonstrated that 400 mg twice-daily sorafenib significantly improved overall survival compared with placebo in more than 600 patients with advanced HCC. At EASL, investigators reported on a subgroup analysis of SHARP participants who experienced failure of prior local or regional therapies.

The subgroup analysis evaluated 158 patients from SHARP who received prior potentially curative treatments including resection (surgery), local ablation, percutaneous ethanol injection (PEI), or radiofrequency ablation (RFA; tumor destruction using heat), as well as 176 who received previous transarterial chemoembolization (TACE).

Among the 158 patients who failed potentially curative treatments, 81 received sorafenib and 77 received placebo. Among the 176 patients who progressed after TACE, 86 received sorafenib and 90 received placebo.

Results

• The median time to progression was significantly longer in the sorafenib group compared with placebo for patients who progressed after potentially curative treatments (median 5.5 vs 2.7 months; HR 0.62) and after TACE (median 5.8 vs 4.0 months; HR 0.57).

• Median overall survival showed a favorable trend towards a benefit with sorafenib for the potentially curative treatments group (11.9 vs 8.8 months; HR 0.79) and for the TACE group (11.9 vs 9.9 months; HR 0.75).

• The most common Grade 3 drug-related treatment-emergent adverse events in the sorafenib arm were diarrhea (9.9% vs 7.0%) and hand-foot skin reactions (8.6% vs 7.0%) for curative treatments vs TACE, respectively.

• No Grade 4 drug-related diarrhea or hand-foot skin reactions were reported.

Conclusion

"Sorafenib improved clinical outcomes compared with placebo in patients with unresectable HCC irrespective of prior therapy," the investigators concluded. "These data are consistent with those in the overall SHARP population and support sorafenib as the new standard of care in HCC patients progressing after loco-regional therapies."

Universitatsklinikum Mainz, Mainz, Germany; CHU - Hopital Saint Andre, Bordeaux Cedex, France; Erasme University Hospital, Brussels, Belgium; University of Michigan, Ann Arbor, MI; Hopital Jean Verdier, Bondy, France; Bayer Schering Pharma, Milan, Italy; Bayer Healthcare Pharmaceuticals, West Haven, CT; Global Clinical Development, Bayer Schering Pharma, Wuppertal, Germany; Barcelona Clinic Liver Cancer Group, Liver Unit, IDIBAPS, Hospital Clinic Barcelona, Barcelona, Spain; Division of Liver Diseases, Mount Sinai School of Medicine, New York, NY.

5/16/08

Reference
P Galle, J Blanc, J-L Van Laethem, and others. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma and prior anti-tumor therapy: a subanalysis from the SHARP trial. 43rd annual meeting of the European Association for the Study of the Liver (EASL 2008). Milan, Italy. April 23-27, 2008.