Theodore H. Welling, III, MD
There has never been as much excitement surrounding systemic therapies for hepatocellular carcinoma (HCC) as the past few years have witnessed, with 1 new drug that was approved, 2 agents pending FDA decisions, and later-stage clinical trials for multiple therapies on the horizon.
In April of this year, the FDA approved regorafenib (Stivarga) as a second-line treatment for patients with HCC following prior sorafenib (Nexavar), which was the only approved systemic therapy in HCC for a decade. The agency will decide by September 24 whether to approve a supplemental biologics license application for nivolumab (Opdivo) as second-line therapy for HCC and an application is pending for lenvatinib (Lenvima) as a first-line therapy.
Each of these advances will be discussed during the 11th Annual Conference of the International Liver Cancer Association, being September 15 to 17 in Seoul, South Korea. In advance of the meeting, Theodore H. Welling, MD, associate professor of surgery, director of the Liver Tumor Program at Perlmutter Cancer Center of NYU Langone Medical Center, shared insight on the top presentations at the meeting, and how he believes the future will look for the treatment of HCC.OncLive: Which presentations at the ILCA meeting will be the most interesting?Welling:
All of the clinical trials or treatment studies that are being presented at the ILCA meeting will be most interesting to the greatest audience; that is specifically related to the immune-oncology trials, as well as the targeted therapy trials. This represents a significant part of the meeting and will be a big focus with respect to them being presented in an oral presentation format with opportunities for discussion and questions.How do you see immunotherapy being incorporated into HCC treatment, with regorafenib now available and the approval of lenvatinib on the horizon?
How immunotherapy fits is really going to be a major area of research. There is a lot of caveats and permutations, which makes the therapy potentially exciting for the treatment of not just patients with liver cancer, but patients with other types of cancers. Can immunotherapy capitalize on other known therapies, where we are already able to generate to some degree a cytotoxic effect or maybe an initial effect on some tumors, and whether or not we can make that effect more pronounced by allowing the immune system to clean up the job, so to speak, in combination with other therapies.
That is where the real excitement exists with respect to how immuno-oncology fits in. The other part is combining and further characterizing, from a biomarker standpoint, which patients are most likely to respond to immuno-oncology therapy. There are other agents that block or accelerate other pathways of the immune response. Therefore, combining this type of therapy with other agents that block either other co-inhibitory pathways or combining with other agents that maybe accelerate other pathways of the immune response is another area of research. What is the current state of liver cancer treatment, and what are some other systemic advancements on the horizon?
The other areas with respect to liver cancer are somewhat similar to what’s being done in some other cancers. That is to evaluate the tumors themselves and characterize the mutational profile or the transcriptomic profile and identify subsets of patients who might benefit from particular therapies.
One example—and this is being tested, evaluated, and presented in some presentations at the ILCA meeting—is targeting FGFR4 and its ligand FGF19. There are a couple of trials evaluating this pathway. Depending again on the subset of patients, certainly, some patients can have evidence of activation of this pathway whereas not all patients do. This and other targeted therapies are also in the future of a lot of research in liver cancer. Beyond systemic therapies, what are the biggest trends in liver cancer?
We are understanding how best to apply our existing therapies. There still is some controversy in the field with respect to locoregional therapies; how to best embolize liver cancers. There are certainly techniques such as radioembolization or chemoembolization. There are certainly ways that can be improved upon. Whether or not that can be combined with some of the agents that we are talking about is certainly one area of research, but also best understanding how to use these locoregional therapies is still an active part of research.
Also, how can we best use other therapies, such as resection and transplantation—potentially in the context of how they might be combined with some of these other systemic therapies? These are part of the multidisciplinary nature in the treatment of liver cancer and how they will be best combined is how the research is going. Brought to you in part by Eisai