Background: The combination of atezolizumab and bevacizumab has become the standard first-line systemic therapy for advanced hepatocellular carcinoma (HCC). However, pivotal clinical trials enrolled highly selected populations, excluding patients with comorbidities or clinical conditions frequently encountered in real-world practice, which remain areas of uncertainty with limited guidance.
Objective: To develop a literature review and consensus recommendations on the use of bevacizumab-containing regimens in special populations with advanced HCC, particularly patients underrepresented or excluded from randomised clinical trials.
Methods: This expert consensus was developed using a structured modified Delphi methodology. A multidisciplinary panel of ten hepatologists and clinical oncologists from different institutions formulated clinical questions using the PICO framework across 11 predefined domains related to bevacizumab safety and use. A PRISMA-informed literature review was conducted, prioritising clinical guidelines, randomised trials, meta-analyses and observational studies. Evidence was appraised using the Oxford Centre for Evidence-Based Medicine Levels of Evidence. Recommendations were drafted, reviewed, graded and voted upon through Delphi rounds.
Results: Consensus recommendations were established for all predefined PICO domains, including anticoagulation, antiplatelet therapy, coagulopathies, liver and renal dysfunction, thrombocytopenia, cardiovascular and cerebrovascular disease, age and body weight extremes, procedural considerations and digestive bleeding risk. The panel emphasised individualised, multidisciplinary decision-making, careful patient selection and proactive risk mitigation strategies. Levels of evidence ranged from moderate to low, reflecting the limited representation of these populations in clinical trials.
Conclusion: This expert consensus provides practical, evidence-informed guidance on the use of bevacizumab in special populations with advanced HCC. By addressing common real-world clinical scenarios not adequately covered by existing guidelines, these recommendations aim to promote consistent, safe and individualised application of bevacizumab-based therapy in routine clinical practice.
