Phase II study of bevacizumab and erlotinib in the treatment of advanced hepatocellular carcinoma patients with sorafenib-refractory disease

Invest New Drugs. 2012 Dec;30(6):2384-90. doi: 10.1007/s10637-012-9808-8. Epub 2012 Mar 9.


Background: The combination of bevacizumab (B) and erlotinib (E) has shown promising clinical outcomes as the first-line treatment of advanced HCC patients. We aimed to evaluate the efficacy and safety of using combination of B + E in treating advanced HCC patients who had failed prior sorafenib treatment.

Methods: Eligible advanced HCC patients with documented radiological evidence of disease progression with sorafenib treatment were recruited. All patients received bevacizumab(B) at 10 mg/kg every 2 weeks with erlotinib(E) at 150 mg daily for a maximum of 6 cycles. Response assessments using both RECIST and modified RECIST criteria were performed after every 6 weeks. The primary endpoint was clinical benefit (CB) rate and a Simon two-stage design was employed.

Results: The trial was halted in the first stage according to the pre-set statistical criteria with 10 patients recruited. The median age was 47 years (range, 28-61) and all patients were in ECOG performance status 1. Eighty percent of patients were chronic hepatitis B carriers and all patients had Child A cirrhosis. Among these 10 patients, none of the enrolled patients achieved response or stable disease. The median time-to-progression was 1.81 months (95 % confidence interval [C.I.], 1.08-1.74 months) and overall survival was 4.37 months (95 % C.I., 1.08-11.66 months). Rash (70 %), diarrhea (50 %) and malaise (40 %) were the most commonly encountered toxicities.

Conclusion: The combination of B + E was well tolerated but had no activity in an unselected sorafenib-refractory advanced HCC population. Condensed abstract The combination of bevacizumab and erlotinib had no clinical activity in sorafenib-refractory HCC population.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Carcinoma, Hepatocellular / drug therapy*
  • Drug Resistance, Neoplasm
  • Erlotinib Hydrochloride
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Niacinamide / administration & dosage
  • Niacinamide / analogs & derivatives
  • Phenylurea Compounds / administration & dosage
  • Quinazolines / administration & dosage
  • Sorafenib


  • Antibodies, Monoclonal, Humanized
  • Phenylurea Compounds
  • Quinazolines
  • Niacinamide
  • Bevacizumab
  • Sorafenib
  • Erlotinib Hydrochloride