title: Phase II trial of bevacizumab and erlotinib as a second-line therapy for advanced hepatocellular carcinoma.
abstract: BACKGROUND
  Clinicaltrials.gov #NCT01180959.
  
  
  BACKGROUND
  Early clinical studies of bevacizumab and erlotinib in advanced hepatocellular carcinoma (HCC) have a tolerable toxicity and a promising clinical outcome. We evaluated the efficacy and tolerability of this combination as a second-line therapy for HCC refractory to sorafenib.
  
  
  METHODS
  For this single-arm, Phase II study, we recruited patients with Child-Pugh class A or B liver disease, Eastern Cooperative Oncology Group performance status 0-2, and advanced HCC that was not amenable to surgical or regional therapies and treatment with sorafenib had failed (disease progressed or patient could not tolerate sorafenib). Patients received 10 mg/kg intravenous bevacizumab every 14 days and 150 mg oral erlotinib daily for 28-day cycles until progression. Tumor response was evaluated every two cycles using Response Evaluation Criteria in Solid Tumors. The primary end point was the 16-week progression-free survival rate. Secondary end points included time to progression and overall survival.
  
  
  RESULTS
  A total of 44 patients were enrolled and had a median follow-up time of 33.8 months (95% confidence interval [CI]: 23.5 months - not defined). The 16-week progression-free survival rate was 43% (95% CI: 28%-59%), median time to progression was 3.9 months (95% CI: 2.0-8.3 months), and median overall survival duration was 9.9 months (95% CI: 8.3-15.5 months). Grade 3-4 adverse events included fatigue (13%), acne (11%), diarrhea (9%), anemia (7%), and upper gastrointestinal hemorrhage (7%).
  
  
  CONCLUSIONS
  Bevacizumab plus erlotinib was tolerable and showed a signal of survival benefit in the second-line setting for patients with advanced HCC. Because standard-of-care options are lacking in this setting, further studies to identify predictors of response to this regimen are warranted.
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ahmed O
authors.initials: AO
authors.lastname: Kaseb
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Morris
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Michiko
authors.initials: M
authors.lastname: Iwasaki
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Humaid O
authors.initials: HO
authors.lastname: Al-Shamsi
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Kanwal Pratap Singh
authors.initials: KP
authors.lastname: Raghav
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Girard
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Sheree
authors.initials: S
authors.lastname: Cheung
authors.affiliation: Department of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Van
authors.initials: V
authors.lastname: Nguyen
authors.affiliation: Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Khaled M
authors.initials: KM
authors.lastname: Elsayes
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Lianchun
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Clinical Oncology, Assiut University Hospital, Assiut, Egypt.
authors.forename: Reham
authors.initials: R
authors.lastname: Abdel-Wahab
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Shalaby
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Manal
authors.initials: M
authors.lastname: Hassan
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Hesham M
authors.initials: HM
authors.lastname: Hassabo
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wolff
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Yao
keywords: bevacizumab; erlotinib; hepatocellular carcinoma; second-line therapy; targeted therapy