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

• Published in: Oncology Vol. 85; no. 1; pp. 44 - 52
• Main Authors: Hsu, Chih-Hung, Kang, Yoon Koo, Yang, Tsai-Shen, Shun, Chia-Tung, Shao, Yu-Yun, Su, Wu-Chou, Sandoval-Tan, Jennifer, Chiou, Tzeon-Jye, Jin, Kate, Hsu, Chiun, Cheng, Ann-Lii
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2013
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Asian Continental Ancestry Group; Asian people; Bevacizumab; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Clinical Study; Disease-Free Survival; Drug therapy; Erlotinib Hydrochloride; Female; Humans; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Male; Middle Aged; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Quinazolines - administration & dosage; Quinazolines - adverse effects; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - metabolism; Treatment Outcome; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; Phase II study; Hepatocellular carcinoma; Erlotinib; Bevacizumab
• ISSN: 0030-2414; 1423-0232
• DOI: 10.1159/000350841

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.