Clinical

Sorafenib added to doxorubicin prolongs survival in advanced liver cancer

Last Updated: 2010-11-17 14:25:05 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Combining the multikinase inhibitor sorafenib (Nexavar, Bayer) with doxorubicin improved overall and progression-free survival in patients with advanced hepatocellular carcinoma (HCC) in a phase 2 trial.

In fact, an interim analysis showed such benefit from combination treatment compared with doxorubicin monotherapy that the multinational trial was halted early, researchers led by Dr. Ghassan K. Abou-Alfa report in the November 17th issue of the Journal of the American Medical Association.

The 96 trial subjects had inoperable HCC with an Eastern Cooperative Oncology Group performance status of 0 to 2, Child-Pugh A status, and no prior systemic therapy. They were enrolled between April 2005 and October 2006, with the last follow-up in April 2008.

Dr. Abou-Alfa, from the Memorial Sloan-Kettering Cancer Center, New York, and his colleagues treated all patients with intravenous doxorubicin 60 mg/m� every 3 weeks for a maximum dose of 450 mg/m�. They randomly assigned them to additional treatment with sorafenib 400 mg (n = 47) or placebo (n = 49) twice daily, which were continued until disease progression.

Median time to disease progression was 6.4 months in the doxorubicin plus sorafenib group and 2.8 months in the doxorubicin plus placebo group (hazard ratio 0.5, p = 0.02).

Twenty-five patients in the sorafenib group and 38 in the placebo group died. Median overall survival was 13.7 months and 6.5 months, respectively (HR 0.49, p = 0.006).

The authors note that tumor shrinkage occurred in 62% of patients treated with sorafenib and in 29% of those treated with placebo.

"Adverse effects of doxorubicin plus sorafenib were essentially additive and similar to what would be expected for each drug used as a single agent," they report.

Based on these results, the authors have already started a phase 3 trial of sorafenib plus doxorubicin vs. sorafenib alone.

Sorafenib is approved in the US and Europe for treatment of liver cancer, although the authors note that "the combination of sorafenib and doxorubicin is not yet indicated for routine clinical use." Average cost of doxorubicin in the US is $143 for 200 mg. Sorafenib runs $7,863 for 120 200-mg tablets.

The study was supported by a research grant from Bayer, which also contributed to the study's design, conduct, and data collection.

SOURCE: http://link.reuters.com/qup75q

JAMA 2010;304:2154-2160.