title: Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205.
abstract: OBJECTIVE
  Patients with advanced pancreas cancer present with disease that is poorly responsive to conventional therapies. Preclinical and early clinical evidence has supported targeting the epidermal growth factor receptor (EGFR) signaling pathway in patients with pancreas cancer. This trial was conducted to evaluate the contribution of an EGFR-targeted agent to standard gemcitabine therapy. Cetuximab is a monoclonal antibody against the ligand-binding domain of the receptor.
  
  
  METHODS
  Patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma were randomly assigned to receive gemcitabine alone or gemcitabine plus cetuximab. The primary end point was overall survival. Secondary end points included progression-free survival, time to treatment failure, objective response, and toxicity.
  
  
  RESULTS
  A total of 745 eligible patients were accrued. No significant difference was seen between the two arms of the study with respect to the median survival time (6.3 months for the gemcitabine plus cetuximab arm v 5.9 months for the gemcitabine alone arm; hazard ratio = 1.06; 95% CI, 0.91 to 1.23; P = .23, one-sided). Objective responses and progression-free survival were similar in both arms of the study. Although time to treatment failure was longer in patients on gemcitabine plus cetuximab (P = .006), the difference in length of treatment was only 2 weeks longer in the combination arm. Among patients who were studied for tumoral EGFR expression, 90% were positive, with no treatment benefit detected in this patient subset.
  
  
  CONCLUSIONS
  In patients with advanced pancreas cancer, the anti-EGFR monoclonal antibody cetuximab did not improve the outcome compared with patients treated with gemcitabine alone. Alternate targets other than EGFR should be evaluated for new drug development.
authors.affiliation: Wayne State University, Karmanos Cancer Institute, GI Oncology, Detroit, MI 48201, USA. philipp@karmanos.org
authors.forename: Philip A
authors.initials: PA
authors.lastname: Philip
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Benedetti
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Corless
authors.forename: Ralph
authors.initials: R
authors.lastname: Wong
authors.forename: Eileen M
authors.initials: EM
authors.lastname: O'Reilly
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Flynn
authors.forename: Kendrith M
authors.initials: KM
authors.lastname: Rowland
authors.forename: James N
authors.initials: JN
authors.lastname: Atkins
authors.forename: Barry C
authors.initials: BC
authors.lastname: Mirtsching
authors.forename: Saul E
authors.initials: SE
authors.lastname: Rivkin
authors.forename: Alok A
authors.initials: AA
authors.lastname: Khorana
authors.forename: Bryan
authors.initials: B
authors.lastname: Goldman
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Fenoglio-Preiser
authors.forename: James L
authors.initials: JL
authors.lastname: Abbruzzese
authors.forename: Charles D
authors.initials: CD
authors.lastname: Blanke
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068818:Cetuximab; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D000068818:Cetuximab; D000093542:Gemcitabine