Perioperative camrelizumab plus rivoceranib in resectable hepatocellular carcinoma: translating CARES-009 outcomes into a new therapeutic paradigm

Background: Hepatocellular carcinoma (HCC) is one of the most common causes of malignancy, and recurrence rates are 50–70% even with curative resection, which indicates the necessity to employ an efficient perioperative systemic treatment. Aim: To conclude, regarding the mechanistic rationale and clinical evidence for perioperative camrelizumab (PD-1 inhibitor) and rivoceranib (VEGFR2 inhibitor) in resectable HCC, it is crucial to review CARES-009 and related information to inform clinical practice and research priorities. Results: Camrelizumab overturns T-cell exhaustion, whereas rivoceranib normalizes tumor vasculature and alleviates hypoxia, creating immuno-angiogenic synergy. In CARES-009, perioperative camrelizumab combined with rivoceranib was superior to surgery for event-free survival and primary pathological response in intermediate/high-risk resectable HCC. The favorable antitumor activity and favorable safety profile are supported by evidence from CARES-310 and other immunotherapy-TKI trials in advanced HCC. Translational research demonstrates that immune-angiogenic signatures and circulating tumor DNA can be used to risk-stratify. However, existing evidence is scarce due to poor overall survival outcomes, cohorts mostly driven by hepatitis B virus, and various regional differences in costs and access to drugs. Conclusion: Perioperative camrelizumab plus rivoceranib is a biologically rational and clinically promising agent that can be used to decrease recurrence in high-risk patients who have undergone resection of HCC. Nevertheless, these should be routinely introduced once mature survival, biomarker, real-world, and economic data are available. Once again, current use is best utilized in clinical trials or structured registry models.