TY - JOUR
T1 - Erlotinib Plus Gemcitabine Compared with Gemcitabine Alone in Patients with Advanced Pancreatic Cancer
T2 - A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group
AU - Moore, Malcolm J.
AU - Goldstein, David
AU - Hamm, John
AU - Figer, Arie
AU - Hecht, Joel R.
AU - Gallinger, Steven
AU - Au, Heather J.
AU - Murawa, Pawel
AU - Walde, David
AU - Wolff, Robert A.
AU - Campos, Daniel
AU - Lim, Robert
AU - Ding, Keyue
AU - Clark, Gary
AU - Voskoglou-Nomikos, Theodora
AU - Ptasynski, Mieke
AU - Parulekar, Wendy
N1 - Publisher Copyright:
© 2023 American Society of Clinical Oncology. All rights reserved.
PY - 2023/10/20
Y1 - 2023/10/20
N2 - PURPOSEPatients 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.PATIENTS AND METHODSPatients 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.RESULTSA 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. CONCLUSIONTo 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.
AB - PURPOSEPatients 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.PATIENTS AND METHODSPatients 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.RESULTSA 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. CONCLUSIONTo 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.
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U2 - 10.1200/JCO.22.02770
DO - 10.1200/JCO.22.02770
M3 - Article
C2 - 37847995
AN - SCOPUS:85174750407
SN - 0732-183X
VL - 41
SP - 4714
EP - 4720
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 30
ER -