Adjuvant and Combination Therapies for HCC

The concept of using sorafenib in the adjuvant setting is a bit flawed, since it is being used as more of a chemopreventive approach for patients with hepatocellular carcinoma (HCC), according to Adam C. Yopp, MD. In terms of trials of adjuvant sorafenib, a phase III study that randomized patients after surgical resection or radiofrequency ablation to sorafenib or placebo did not show any improvement in recurrence-free survival. Currently, in the adjuvant setting, there is nothing to offer to patients with HCC, Yopp concludes.

As a hepatologist, Robert G. Gish, MD, FAASLD, stresses the need to treat the underlying disease. If a patient has both liver disease and hepatitis B, it has been shown that suppressing the hepatitis B will delay the time to recurrence and reduce the overall risk of recurrence of the liver disease. Similarly, curing underlying hepatitis C will result in a healthier liver, as well as delay recurrence and decreased the risk of recurrence. More data are needed to understand the risk reduction potential of treating nonalcoholic steatohepatitis (NASH), he adds.

The concept of combining chemoembolization with an antiangiogenic agent is based on the fact that angiogenesis is actually a biomarker for a poor prognosis in HCC. If a patient has higher VEGF levels they are more likely to do poorly, regardless of any subsequent therapy, states Jeff Geschwind, MD. Additionally, within 24 to 36 hours following chemoembolization, there is a significant rise in VEGF levels in the blood, suggesting there could be synergy with an antiangiogenic agent, such as sorafenib.

This theory has been tested in several studies, including the ECOG 1208 and SPACE trials. The combination may be effective in patients with liver-dominant disease with some extrahepatic disease or macrovascular invasion. Many trials throughout the world have established a safety profile of the combination, states Geschwind. It doesn’t matter whether it is administered continuously, sequentially, or interrupted, he says; the bottom line is that these treatments are safe to use in combination.