Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group.
OBJECTIVE
Patients with advanced pancreatic cancer have a poor prognosis and there have been no improvements in survival since the introduction of gemcitabine in 1996. Pancreatic tumors often overexpress human epidermal growth factor receptor type 1 (HER1/EGFR) and this is associated with a worse prognosis. We studied the effects of adding the HER1/EGFR-targeted agent erlotinib to gemcitabine in patients with unresectable, locally advanced, or metastatic pancreatic cancer.


METHODS
Patients were randomly assigned 1:1 to receive standard gemcitabine plus erlotinib (100 or 150 mg/d orally) or gemcitabine plus placebo in a double-blind, international phase III trial. The primary end point was overall survival.


RESULTS
A total of 569 patients were randomly assigned. Overall survival based on an intent-to-treat analysis was significantly prolonged on the erlotinib/gemcitabine arm with a hazard ratio (HR) of 0.82 (95% CI, 0.69 to 0.99; P = .038, adjusted for stratification factors; median 6.24 months v 5.91 months). One-year survival was also greater with erlotinib plus gemcitabine (23% v 17%; P = .023). Progression-free survival was significantly longer with erlotinib plus gemcitabine with an estimated HR of 0.77 (95% CI, 0.64 to 0.92; P = .004). Objective response rates were not significantly different between the arms, although more patients on erlotinib had disease stabilization. There was a higher incidence of some adverse events with erlotinib plus gemcitabine, but most were grade 1 or 2.


CONCLUSIONS
To our knowledge, this randomized phase III trial is the first to demonstrate statistically significantly improved survival in advanced pancreatic cancer by adding any agent to gemcitabine. The recommended dose of erlotinib with gemcitabine for this indication is 100 mg/d.
Moore
Malcolm J
MJ
Division of Medical Oncology, Princess Margaret Hospital, Toronto, Canada. malcolm.moore@uhn.on.ca
Goldstein
David
D
Hamm
John
J
Figer
Arie
A
Hecht
Joel R
JR
Gallinger
Steven
S
Au
Heather J
HJ
Murawa
Pawel
P
Walde
David
D
Wolff
Robert A
RA
Campos
Daniel
D
Lim
Robert
R
Ding
Keyue
K
Clark
Gary
G
Voskoglou-Nomikos
Theodora
T
Ptasynski
Mieke
M
Parulekar
Wendy
W
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004311:Double-Blind Method; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D007390:International Agencies; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010919:Placebos; D011379:Prognosis; D011799:Quinazolines / Q000008:administration & dosage; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
D010919:Placebos; D011799:Quinazolines; D003841:Deoxycytidine; D000069347:Erlotinib Hydrochloride; D000093542:Gemcitabine