Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer.
OBJECTIVE
Treatment with gemcitabine provides modest benefits in patients with metastatic pancreatic cancer. The addition of erlotinib to gemcitabine shows a small but significant improvement in overall survival (OS) versus gemcitabine alone. Phase II results for bevacizumab plus gemcitabine provided the rationale for a phase III trial of gemcitabine-erlotinib plus bevacizumab or placebo.


METHODS
Patients with metastatic pancreatic adenocarcinoma were randomly assigned to receive gemcitabine (1,000 mg/m(2)/week), erlotinib (100 mg/day), and bevacizumab (5 mg/kg every 2 weeks) or gemcitabine, erlotinib, and placebo in this double-blind, phase III trial. Primary end point was OS; secondary end points included progression-free survival (PFS), disease control rate, and safety.


RESULTS
A total of 301 patients were randomly assigned to the placebo group and 306 to the bevacizumab group. Median OS was 7.1 and 6.0 months in the bevacizumab and placebo arms, respectively (hazard ratio [HR], 0.89; 95% CI, 0.74 to 1.07; P = .2087); this difference was not statistically significant. Adding bevacizumab to gemcitabine-erlotinib significantly improved PFS (HR, 0.73; 95% CI, 0.61 to 0.86; P = .0002). Treatment with bevacizumab plus gemcitabine-erlotinib was well tolerated: safety data did not differ from previously described safety profiles for individual drugs.


CONCLUSIONS
The primary objective was not met. The addition of bevacizumab to gemcitabine-erlotinib did not lead to a statistically significant improvement in OS in patients with metastatic pancreatic cancer. PFS, however, was significantly longer in the bevacizumab group compared with placebo. No unexpected safety events were observed from adding bevacizumab to gemcitabine-erlotinib.
Van Cutsem
Eric
E
University Hospital Gasthuisberg/Leuven, Digestive Oncology Unit, Herestraat 49, B-3000 Leuven, Belgium. eric.vancutsem@uz.kuleuven.ac.be
Vervenne
Walter L
WL
Bennouna
Jaafar
J
Humblet
Yves
Y
Gill
Sharlene
S
Van Laethem
Jean-Luc
JL
Verslype
Chris
C
Scheithauer
Werner
W
Shang
Aijing
A
Cosaert
Jan
J
Moore
Malcolm J
MJ
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000069347:Erlotinib Hydrochloride; D006801:Humans; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D000093542:Gemcitabine
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D011799:Quinazolines; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069347:Erlotinib Hydrochloride; D000093542:Gemcitabine