Interview with Anne-Laure Grindel & Nathalie Fretellier, Researchers in Guerbet
Q1. What is Guerbet’s current focus in cancer research?
Hepatocellular Carcinoma, or HCC, is the most primary liver cancer. It is now the fifth cause of cancer in adults and the third cause of cancer-related death1. Despite multiple treatment methods, incidence and mortality rates continue to rise. Currently, only surgical transplantation and tumor resection are considered as curative treatments. Unfortunately, only 30% of patients can benefit from these treatments. Other treatment modalities are available for higher-stage HCC, like drugs (e.g. Sorafenib), interventional radiology (e.g. ablation, transarterial chemoembolization or microwaves) or immunotherapy with immune checkpoint inhibitors.
Because none of those treatments are efficient enough to treat most patients with an unresectable liver tumor, our team is currently working on the interest of combining treatments, especially interventional radiology techniques with immune checkpoint inhibitors.
Q2. What is the background of this study and why this specific research?
Immunotherapy (IT) is a very promising treatment in patients with metastatic disease by stimulating an effective systemic immune response against tumor cells. Several studies have demonstrated remarkable complete responses. However, IT has only been shown to be effective in certain tumor types, such as melanoma, renal cell carcinoma and non-small cell lung cancers. In patients with end-stage HCC, only 20% of patients respond to monotherapy3. Moreover, serious systemic adverse events are also commonly reported. Combinatorial immunotherapy approaches are therefore likely to be the most viable strategy for improving responses and outcomes for patients.
Locoregional treatments such as cTACE induce inflammation and release of tumor-associated antigens, stimulating the immune system and helping to create an anti-tumor microenvironment4,5. However, this effect alone appears insufficient to generate consistent protective or curative antitumor immunity against distant metastases. If combined with IT, we can expect an increase in overall outcomes6.
Our objective is to improve patient care by increasing the response rate and efficacy but also tolerance to treatment.
Q3. What are the main findings so far and how long will the research last?
Interest in combining treatments is new for Guerbet, and clinical trials are currently recruiting to study the safety and efficacy of combined interventional radiology and immune checkpoint immunotherapy treatment in HCC patients.
The safety of such combinations has already been demonstrated in HCC patients. Tremelimumab, an anti-CTLA-4 immune checkpoint inhibitor, has a good safety record when combined with either thermal ablation or partial TACE in HCC patients7. These results are encouraging, and the demonstration of potential improved efficacy of this kind of combination versus treatments alone is now necessary to improve the management of patients with HCC. It will take several years to effectively demonstrate the efficacy and safety of these new treatment modalities.
Q4. What are the next steps for future research as a result of this work?
We are currently investigating the association between locoregional treatments, especially cTACE of unresectable HCC, with immunotherapy, in several preclinical models. The next steps of our research will be to evaluate the safety and efficacy of the best combination in clinical trials.
- Goodarzi, E., et al. "Global incidence and mortality of liver cancers and its relationship with the human development index (HDI): an ecology study in 2018." World Cancer Research Journal6 (2019): 12.
- Idée, Jean-Marc, and Boris Guiu. "Use of Lipiodol as a drug-delivery system for transcatheter arterial chemoembolization of hepatocellular carcinoma: a review." Critical reviews in oncology/hematology 88.3 (2013): 530-549.
- Huppert, Laura A., John D. Gordan, and Robin Kate Kelley. "Checkpoint inhibitors for the Treatment of advanced Hepatocellular Carcinoma." Clinical Liver Disease 15.2 (2020): 53.
- Tampaki, Maria, et al. "Circulating biomarkers of hepatocellular carcinoma response after locoregional treatments: New insights." World journal of hepatology 7.14 (2015): 1834.
- Lee, Hae Lim, et al. "Inflammatory cytokines and change of Th1/Th2 balance as prognostic indicators for hepatocellular carcinoma in patients treated with transarterial chemoembolization." Scientific reports 9.1 (2019): 1-8.
- Dendy, Meaghan S., et al. "Locoregional therapy, immunotherapy and the combination in hepatocellular carcinoma: future directions." Liver cancer 8.5 (2019): 326-340.
- Duffy, Austin G., et al. "Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma." Journal of hepatology 66.3 (2017): 545-551.