Daneng Li, MD

Patients with advanced HCC encompass a heterogenous group ranging from those with liver-predominant tumors refractory to locoregional therapies, to multilobed disease, to those with macrovascular invasion and/or extrahepatic spread. Prior clinical trials studying combination locoregional therapies combined with systemic therapy for patients with advanced HCC have encountered difficulties given such diverse patient populations.

Despite the possible benefits of better controlling tumors within the liver with locoregional therapies in patients with advanced HCC, prior studies combining liver-directed therapy with transarterial chemoembolization or radioembolization in combination with sorafenib (Nexavar, Bayer) vs. sorafenib alone among these patients have not shown any significant difference in OS.

In the current phase 3 study, the combination of lenvatinib plus transarterial chemoembolization achieved significant improvement in OS compared with lenvatinib alone in patients with advanced HCC. Although the investigators should be commended for their effort in trying to address this complex and heterogenous patient population with use of multimodality treatments, many questions remain regarding the true applicability of the trial results to clinical practice. First, this study involved an overwhelming Asian patient population extensively with hepatitis B-associated HCC, limiting generalizability of results. In addition, the complete tumor characteristics of patients enrolled onto the trial and whether a majority had liver-predominant disease remain unclear. Also unclear is the magnitude of benefit of transarterial chemoembolization plus systemic therapy in patients without liver-predominant advanced HCC.

As systemic therapy options for patients with advanced HCC continue to evolve with further improvements in response rates and OS with systemic therapy alone, ongoing and future trial results exploring various locoregional therapies in combination with newer systemic therapies are awaited. Ultimately, until these data are available, the decision for combination multimodality therapy is still best made in the setting of discussions among the various multidisciplinary team members involved in treating patients with advanced HCC.

Shikha Jain, MD, FACP

Patients with metastatic HCC are a heterogeneous population and this malignancy has historically been challenging to treat.

This study looked at patients in China, where there is high incidence of this pathology and high risk for mortality. This is also true in the United States, where HCC is the most rapidly increasing malignancy in men and women. Incidence rates have more than tripled since 1980.

Liver and intrahepatic bile duct cancers are the seventh most common cause of cancer death for U.S. women and fifth most common for U.S. men. Patients often present at a late stage and are not curable at initial presentation.

Historically, options for therapeutic intervention have been relatively limited. This study looked at an interesting and potentially useful combination of local therapy utilizing transarterial chemoembolization, with or without the addition of lenvatinib, to determine if a combination approach may provide some benefit to this challenging patient population.

This study may have a significant impact on the future of cancer care for patients with HCC; however, it is important to note that more studies are needed. The patient population in this study was predominantly Asian, with many having hepatitis B virus-associated HCC. Further studies also are needed to determine whether patients without liver-predominant hepatocellular carcinoma would benefit from this type of combination therapy.

Combination therapy in HCC has been a challenge with mixed results, and this may be a future therapeutic option in this difficult-to-treat population. However, more studies will be needed to better understand if this data can be reproduced in different populations and how this type of combination therapy may be incorporated into future lines of therapy.