title: Bevacizumab with erlotinib as first-line therapy in Asian patients with advanced hepatocellular carcinoma: a multicenter phase II study.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Hsu
authors.forename: Yoon Koo
authors.initials: YK
authors.lastname: Kang
authors.forename: Tsai-Shen
authors.initials: TS
authors.lastname: Yang
authors.forename: Chia-Tung
authors.initials: CT
authors.lastname: Shun
authors.forename: Yu-Yun
authors.initials: YY
authors.lastname: Shao
authors.forename: Wu-Chou
authors.initials: WC
authors.lastname: Su
authors.forename: Jennifer
authors.initials: J
authors.lastname: Sandoval-Tan
authors.forename: Tzeon-Jye
authors.initials: TJ
authors.lastname: Chiou
authors.forename: Kate
authors.initials: K
authors.lastname: Jin
authors.forename: Chiun
authors.initials: C
authors.lastname: Hsu
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People; D000068258:Bevacizumab; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D011799:Quinazolines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt