Neoadjuvant Immunotherapy for Hepatocellular Carcinoma

Abstract

Thomas U Marron,1– 7 Myron Schwartz,1– 4,6,7 Virginia Corbett,1,3,5– 7 Miriam Merad1– 7 1The neoAdjuvant Research Group to Evaluate Therapeutics (TARGET), Icahn School of Medicine at Mount Sinai, New York, NY, USA; 2Early Phase Trials Unit, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 3Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 4Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 5Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 6Center of Excellence for Liver and Bile Duct Cancer, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 7Liver Cancer Program, Division of Liver Diseases and RM Transplant Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USACorrespondence: Thomas U Marron, Email [email protected]: The treatment paradigm for hepatocellular carcinoma (HCC) had been stagnant until recently, with new combinations of targeted and immunotherapies entering the first- and second-line setting for patients with advanced disease. This improvement in therapeutic options is well timed given the rise in rates of HCC globally; additionally, screening high-risk patients has also led to an increase in detection of early HCC lesions, identifying patients who can be treated with curative intent approaches such as surgery. Unfortunately, the vast majority of patients who undergo surgical resection develop recurrent HCC, either due to disease recurrence from residual micrometastatic disease or de novo primaries, and there are no perioperative therapies that have demonstrated the ability to significantly improve survival for these patients. Given the survival benefit that immunotherapy has imparted to patients with advanced HCC, and recent studies in other tumor types demonstrating perioperative—in particular neoadjuvant—immunotherapy significantly improves outcomes, there is substantial interest in neoadjuvant immunotherapy for patients with resectable HCC. Three recently reported small studies looking at anti-PD-1 antibodies alone or in combination have demonstrated significant pathologic response to brief pre-operative interventions, and support exploring this approach in larger registrational studies. With these developments the clinical outlook for HCC patients, with both early and advanced disease, is rapidly improving.Keywords: immunotherapy, neoadjuvant therapy, perioperative therapy

Keywords

• immunotherapy
• neoadjuvant therapy
• perioperative therapy