Dr Finn: We have a very exciting meeting this weekend at ILCA in Seoul, Korea. There have been several interesting presentations already on the first day and there has been a lot of interest in immunotherapies being developed for liver cancer. We have had some lectures on the basic biology of the immune system and its relationship to the development of cancer. Also this morning, we had several lectures about the importance of management of hepatitis and how that is changing the natural history of liver cancer, around the world and certainly here in Asia. That relates to hepatitis B as well as the new agents being applied to the management of hepatitis C. We also had some very original papers presented including original research on biomarkers involved in identifying response to sorafenib. We have also seen some data at this meeting about new imaging modalities for liver cancer, and during the weekend, we will see some additional studies and some primary clinical trial results. One of those is LiverTag, as well as updates of the immunotherapy study involving nivolumab. We will see several very interesting studies with molecules from H3BioPharma, Blueprint Pharma and others evaluating small molecule inhibitors of the fibroblast growth factor receptor family, the FGFR-4 inhibitors. We will also have the results from the pivotal study of lenvatinib versus sorafenib in the frontline therapy of liver cancer, and also some biomarker data from the STORM study, BioSTORM. The STORM study was an adjuvant study evaluating sorafenib after resection for liver cancer. Evaluating the tissue from that study will be very interesting to hear about at this meeting.

 

Dr Finn: This year’s ILCA Conference is a very exciting meeting. We are glad to be back in Asia. Certainly, liver cancer is a major health problem around the world, but even moreso in Asia. There is a lot of excellent research coming out of Asia that we are glad to highlight at the meeting. I have mentioned some of the important presentations – some of the first data with fibroblast growth factor receptor (FGFR-4) inhibitors; and the initial data from LiverTag, a novel therapeutic that was evaluated in liver cancer, which unfortunately was a negative study but helping us learn more about the signals that might come out of that. ILCA has always been a multidisciplinary organization, so we are seeing clinical studies, basic science studies, surgical and radiological studies and pathology – all of the relevant disciplines in liver cancer are represented at our meeting and it is off to an excellent start.

 

Dr Finn: Liver cancer is obviously a very difficult disease to treat. There has been great emphasis on developing molecular targeted drugs in this disease. For the past ten years, we have had sorafenib, an oral multikinase inhibitor, against the VEGF receptors as well as other proteins. That established proof-of-concept that we can improve survival with a systemic drug. That had never been shown before. For the past ten years, we have been trying to do better, but unfortunately those efforts have all been negative until recently. Last year, we saw data with regorafenib, another multikinase inhibitor that was the first drug to improve survival after progression on sorafenib, a real unmet need. That drug has recently been approved in the United States and elsewhere in the world. Now, we have the sequence from sorafenib to regorafenib. Recent analyses presented at GI-ASCO showed that in the sequence where patients start with sorafenib and transition to regorafenib at progression, we saw survival of 26 months in that population, which is a very impressive number. Recently, at ASCO and being presented again here at ILCA, we saw the results of the REFLEX study comparing sorafenib to lenvatinib.  Lenvatinib is a multikinase inhibitor against the VEGF family as well as the fibroblast growth factor receptor family. The study was aimed at non-inferiority, and it showed that lenvatinib was non-inferior to sorafenib with some toxicity differences. There was some increase in response rate and time-to-progression and PFS with lenvatinib, but we are waiting to see more data and analyses from those studies.

 

Dr Finn: As you have said, the impact of immuno-oncology agents has been quite profound, certainly in very difficult diseases to treat such as melanoma and lung cancer. It seems like every week we are learning more about these drugs in cancer medicine, Hodgkin’s disease, head and neck cancer, bladder cancer. The CHECKMATE 040 study was a fairly large single-arm study evaluating nivolumab in liver cancer. Both cohorts that had prior sorafenib and those that were sorafenib-na?ve are showing very provocative data with response rates of 15-20% depending on the cohort. In the second-line, there is survival of about 15 months. Given that single-arm data, we are now awaiting the results of the randomized study of sorafenib versus nivolumab. In the United States, nivolumab as a single agent is going to be reviewed by the FDA based on that single-arm study. We also know now that pembrolizumab, another PD-1 antibody, is being evaluated in the second-line in a randomized study versus placebo. There are other PD-1 inhibitors moving into the space. There is certainly interest in combining these with other agents. I would hope that we have a rationale to combine them rather than just saying standard of care then add-on a new drug. As it turns out, many of these multikinase inhibitors do affect the immune milieu and the surrounding immune environment of these tumors. We have seen in kidney cancer that the combination of lenvatinib and pembrolizumab is showing very significant activity, so we look forward to launching those types of studies in liver cancer with lenvatinib and regorafenib and others.