Novel immunotherapy combinations in clinical trials for hepatocellular carcinoma: Will they shape the future treatment landscape?
Claudia Angela Maria Fulgenzi
, Antonio D’Alessio
, Olabisi Ogunbiyi
, Coskun O. Demirtas
, Alessandra Gennari
, Alessio Cortellini
, show all
Received 18 Mar 2022, Accepted 28 Apr 2022, Accepted author version posted online: 04 May 2022
Underlying liver disease and the intrinsic chemoresistance have historically hampered the development of efficacious treatments in HCC. However, in the last few years, immunotherapy-based combinations have emerged as efficacious therapeutic strategy in this setting. This paper critically summarises the recent therapeutic progress in the systemic treatment of HCC.
Area covered
This paper examines the preclinical rationale of the following combinations in HCC: dual checkpoint inhibitors, immune checkpoint inhibitors plus anti-angiogenic agents, and immune checkpoint inhibitors plus tyrosine kinase inhibitors. Results of recent clinical studies are presented, along with a brief overview of ongoing and future trials. At the end of each sub session, the authors critically review current issues mainly concerning the safety and clinical applicability of each approach.
Expert opinion
The approval of atezolizumab plus bevacizumab and the positive results of the HIMALAYA trial have broadened the therapeutic scenario for advanced HCC, opening, at the same time, new challenges for clinicians and researchers. First of all, predictive biomarkers to allocate patients to the best treatment are eagerly required; second specific studies are urgently needed to define the use of new combinations in patients usually excluded from clinical trials: e.g., those with deranged liver function, HIV or transplant recipients. Finally, with new combinations being translated into earlier stages, profound changes are soon expected in the adjuvant and neoadjuvant setting.