Neoadjuvant and adjuvant systemic therapy in HCC: Current status and the future

Author:

Singal Amit G.1ORCID,Yarchoan Mark2ORCID,Yopp Adam3ORCID,Sapisochin Gonzalo4,Pinato David J.56ORCID,Pillai Anjana7ORCID

Affiliation:

1. Department of Medicine, UT Southwestern Medical Center, Dallas, Texas, USA

2. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

3. Department of Surgery, UT Southwestern Medical Center, Dallas, Texas, USA

4. Department of Surgery, University of Toronto and University Health Network, Toronto, Ontario, Canada

5. Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, UK

6. Department of Translational Medicine, Division of Oncology, University of Piemonte Orientale, Novara, Italy

7. Department of Medicine, University of Chicago, Chicago, Illinois, USA

Abstract

Surgical therapies in patients with early-stage HCC can afford long-term survival but are often limited by the continued risk of recurrence, underscoring an interest in (neo)adjuvant strategies. Prior attempts at adjuvant therapy using tyrosine kinase inhibitors failed to yield significant improvements in recurrence-free survival or overall survival. Advances in the efficacy of systemic therapy options, including the introduction of immune checkpoint inhibitors, have fueled renewed interest in this area. Indeed, the IMBrave050 trial recently demonstrated significant improvements in recurrence-free survival with 1 year of adjuvant atezolizumab plus bevacizumab in high-risk patients undergoing surgical resection or ablation, with several other ongoing trials in this space. There is a strong rationale for consideration of the administration of these therapies in the neoadjuvant setting, supported by early clinical data demonstrating high rates of objective responses, although larger trials examining downstream outcomes are necessary, particularly considering the possible risks of this strategy. In parallel, there has been increased interest in using systemic therapies as a bridging or downstaging strategy for liver transplantation. Current data suggest the short-term safety of this approach, with acceptable rates of rejection, so immunotherapy is not considered a contraindication to transplant; however, larger studies are needed to evaluate the incremental value of this approach over locoregional therapy. Conversely, the use of immunotherapy is currently discouraged after liver transplantation, given the high risk of graft rejection and death. The increasing complexity of HCC management and increased consideration of (neo)adjuvant strategies highlight the critical role of multidisciplinary care when making these decisions.

Publisher

Ovid Technologies (Wolters Kluwer Health)

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