Bevacizumab with Erlotinib as First-line Therapy in Asian Patients with Advanced Hepatocellular Carcinoma: A Multicenter Phase II Study

Objectives: The bevacizumab/erlotinib combination was reported with high clinical activity for advanced hepatocellular carcinoma (HCC) by a phase II study conducted in the USA. This multicenter study across several Asian countries was to evaluate the safety and efficacy of the combination in this population. Methods: Patients with histology-proven HCC, advanced disease and Child-Pugh class A liver function received bevacizumab 5 mg/kg intravenously every 2 weeks and erlotinib 150 mg/day orally as first-line therapy. The primary end point was progression-free survival at 16 weeks (PFS-16W). The expression of epidermal growth factor receptor (EGFR), phospho-AKT and vascular endothelial growth factor, the microvessel density and the EGFR gene copy number in HCC tissues were correlated with treatment efficacy. Results: Fifty-one patients were enrolled. The PFS-16W was 35.3% (95% CI 22.4-49.9), the median PFS was 2.9 months (95% CI, 1.3-4.4) and the median overall survival was 10.7 months (95% CI, 6.2-15.2). Grade 3/4 toxicities were uncommon, including rash, acne (10% each), diarrhea (6%) and gastrointestinal bleeding (4%). None of the evaluated biomarkers correlated with disease control or PFS. Conclusions: Bevacizumab plus erlotinib showed good tolerability and modest activity in this Asian cohort. Further studies are warranted to identify the predictive biomarkers of this combination. Copyright (C) 2013 S. Karger AG, Basel.