Dr. Abou-Alfa on Doxorubicin Plus Sorafenib in Liver Cancer

Ghassan K. Abou-Alfa, MD, Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, describes a study looking at sorafenib plus doxorubicin compared with doxorubicin alone in patients with advanced hepatocellular carcinoma (HCC).

The phase III randomized trial showed benefit in overall survival (OS), progression-free survival (PFS), and time to progression (TTP). Median OS was 13.7 months in the doxorubicin-sorafenib arm (95% CI, 8.9--not reached) and 6.5 months (95% CI, 4.5-9.9; P = .006) in the doxorubicin-placebo arm. PFS also showed benefit: 6.0 months (95% CI, 4.6-8.6) versus 2.7 months (95% CI, 1.4-2.8; P = .006). Median TTP was 6.4 months (95% CI, 4.8-9.2) compared to 2.8 months (95% CI, 1.6-5) (P = .02).

Abou-Alfa notes that research must be completed to determine whether the benefit is related to sorafenib or if true synergistic activity is taking place. The ASK1 molecule works well with a RAF kinase inhibitor such as sorafenib and is crucial for an anthracycline such as doxorubicin to cause apoptosis.