Efficacy of bevacizumab plus erlotinib for advanced hepatocellular carcinoma and predictors of outcome: final results of a phase II trial.
OBJECTIVE
A phase II study was performed to evaluate the efficacy and tolerability of bevacizumab and erlotinib in advanced hepatocellular carcinoma (HCC) patients, and to investigate clinical and molecular predictors of outcome.


METHODS
59 patients with advanced HCC received 10 mg/kg i.v. of bevacizumab every 14 days and 150 mg p.o. of erlotinib daily. The primary endpoint was progression-free survival (PFS) at 16 weeks. Clinical characteristics and plasma biomarkers expression levels were analyzed.


RESULTS
PFS at 16 weeks was 64% (95% CI 51-76): 14 patients achieved partial response (24%), 33 had stable disease (56%), 6 progressed (10%), and 6 were not evaluable (10%). Median overall survival was 13.7 months (95% CI 9.6-19.7), and median PFS was 7.2 months (95% CI 5.6-8.3). Grade 3-4 adverse events included fatigue (30%), diarrhea (17%), hypertension (14%), elevated transaminases (12%), and gastrointestinal hemorrhage (10%). High plasma angiopoietin-2, epidermal growth factor receptor, and endothelin-1, and lack of acneiform rash were associated with poor outcome.


CONCLUSIONS
The combination of bevacizumab with erlotinib achieved encouraging results in patients with advanced HCC. Current correlatives may help to guide future HCC studies.
Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. akaseb@mdanderson.org
Ahmed O
AO
Kaseb
E
E
Garrett-Mayer
J S
JS
Morris
L
L
Xiao
E
E
Lin
G
G
Onicescu
M M
MM
Hassan
H M
HM
Hassabo
M
M
Iwasaki
F L
FL
Deaton
J L
JL
Abbruzzese
M B
MB
Thomas
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042702:Angiopoietin-2 / Q000097:blood; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000097:blood; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects
D042702:Angiopoietin-2; D061067:Antibodies, Monoclonal, Humanized; D011799:Quinazolines; D000068258:Bevacizumab; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors