Adjuvant and neoadjuvant therapies for hepatocellular carcinoma

Immune-oncology based regimens have shown efficacy in advanced hepatocellular carcinoma and have been implemented as standard of care as first line therapy. Their efficacy, including high response rates, and safety justifies their evaluation in earlier disease stages. Following negative results for adjuvant sorafenib in the global STORM trial in 2015, four global phase 3 trials, featuring different immune checkpoint inhibitor combinations, entered in parallel the race in the adjuvant setting. The IMbrave050 trial, comparing adjuvant atezolizumab in combination with bevacizumab to active surveillance following curative-intent resection or ablation, was the first to report, fast-tracking the results of the first interim analysis and demonstrating an improvement in recurrence free survival. The trial has provoked a discussion on the horizon of expectations from adjuvant treatment and the clinical relevance of efficacy endpoints. Moreover, major pathological responses reported from early phase 2 data in the neoadjuvant setting provide a strong rational for the evaluation of these concepts in phase 3 trials. In this review, we summarize current evidence and outline future directions for systemic therapies in early-stage hepatocellular carcinoma.