Premium
Challenges and Opportunities in the Clinical Development of Immune Checkpoint Inhibitors for Hepatocellular Carcinoma
Author(s) -
Flynn Michael J.,
Sayed Anwar A.,
Sharma Rohini,
Siddique Abdul,
Pinato David J.
Publication year - 2019
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.30337
Subject(s) - medicine , hepatocellular carcinoma , clinical trial , drug development , ipilimumab , intensive care medicine , disease , immunotherapy , immune system , drug , oncology , immunology , pharmacology
After a decade of stagnation in drug development, therapeutic reversal of immune‐exhaustion with immune checkpoint inhibitors (ICPIs) has been shown to be effective in advanced hepatocellular carcinoma (HCC). The clinical development of novel ICPIs continues at a rapid pace, with more than 50 clinical trials of immunotherapeutic agents registered as of May 2018 for this indication. The development of ICPI is particularly challenging in patients with HCC, a population with unique features which impact on safety and efficacy of immune‐modulating therapies. In this review, we discuss the biological foundations supporting the development of ICPIs across the advancing stages of HCC, focusing on the rational positioning of ICPIs across the various Barcelona‐Clinic Liver Cancer (BCLC) stages of the disease. Translational studies should guide adequate prioritization of those therapeutic agents and combination strategies which are most likely to achieve patient benefit based on solid mechanistic and clinical justifications.