Dr Franses on the Need for Prospective Data in Second-Line HCC and Beyond

Joseph Franses, MD, PhD, assistant professor, medicine, University of Chicago Medicine Comprehensive Cancer Center, discusses the need for more prospective research to answer remaining questions and expand options in the second-line setting and beyond for patients with hepatocellular carcinoma (HCC).

Improving treatment options in the second line and beyond for patients whose disease progresses following first-line therapy is a key focus within the treatment landscape, Franses begins. He goes on to note that additional data could help address unanswered questions and guide treatment decision-making in the current first-line setting. A considerable number of patients in this setting remain fit enough to pursue additional treatment options if their disease progresses on first-line therapy, Franses states.

In the absence of new clinical trial data, Franses says that there are some approved regimens that can be utilized off-label, though many were initially studied for first-line settings, Franses says. Determining the appropriate sequence of these treatments is necessary to treat patients effectively, he notes. For example, in the absence of dose-limiting toxicities for immunotherapy, it is common practice to use lenvatinib (Lenvima) following frontline immunotherapy.

Numerous second-line studies are underway, Franses continues. These include approaches that combine alternative dual immunotherapies, such as anti–PD-1 plus anti–TGF-beta pathway inhibitors. Precision medicine strategies are also being explored for novel targets like beta-catenin-driven tumors, which account for approximately one-third of HCC cases, he expands. Additionally, there are efforts to target the c-Myc oncogene, which drives a significant proportion of HCC; however, it is not yet identifiable through genomic markers. Research is ongoing to develop biomarkers for these targets, Franses says.

These second-line and beyond studies are vital in providing the data needed to refine and expand treatment options, he emphasizes. As the field progresses, the insights gained from these trials will likely lead to improved therapeutic strategies, enhancing patient outcomes in advanced stages of disease, Franses concludes.