title: Effect of Chemoradiotherapy vs Chemotherapy on Survival in Patients With Locally Advanced Pancreatic Cancer Controlled After 4 Months of Gemcitabine With or Without Erlotinib: The LAP07 Randomized Clinical Trial.
abstract: OBJECTIVE
  In locally advanced pancreatic cancer, the role of chemoradiotherapy is controversial and the efficacy of erlotinib is unknown.
  
  
  OBJECTIVE
  To assess whether chemoradiotherapy improves overall survival of patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine-based induction chemotherapy and to assess the effect of erlotinib on survival.
  
  
  METHODS
  In LAP07, an international, open-label, phase 3 randomized trial, 449 patients were enrolled between 2008 and 2011. Follow-up ended in February 2013.
  
  
  METHODS
  In the first randomization, 223 patients received 1000 mg/m2 weekly of gemcitabine alone and 219 patients received 1000 mg/m2 of gemcitabine plus 100 mg/d of erlotinib. In the second randomization involving patients with progression-free disease after 4 months, 136 patients received 2 months of the same chemotherapy and 133 underwent chemoradiotherapy (54 Gy plus capecitabine).
  
  
  METHODS
  The primary outcome was overall survival from the date of the first randomization. Secondary outcomes were the effect of erlotinib and quality assurance of radiotherapy on overall survival, progression-free survival of gemcitabine-erlotinib and erlotinib maintenance with gemcitabine alone at the second randomization, and toxic effects.
  
  
  RESULTS
  A total of 442 of the 449 patients (232 men; median age, 63.3 years) enrolled underwent the first randomization. Of these, 269 underwent the second randomization. Interim analysis was performed when 221 patients died (109 in the chemoradiotherapy group and 112 in the chemotherapy group), reaching the early stopping boundaries for futility. With a median follow-up of 36.7 months, the median overall survival from the date of the first randomization was not significantly different between chemotherapy at 16.5 months (95% CI, 14.5-18.5 months) and chemoradiotherapy at 15.2 months (95% CI, 13.9-17.3 months; hazard ratio [HR], 1.03; 95% CI, 0.79-1.34; P = .83). Median overall survival from the date of the first randomization for the 223 patients receiving gemcitabine was 13.6 months (95% CI, 12.3-15.3 months) and was 11.9 months (95% CI, 10.4-13.5 months) for the 219 patients receiving gemcitabine plus erlotinib (HR, 1.19; 95% CI, 0.97-1.45; P = .09; 188 deaths vs 191 deaths). Chemoradiotherapy was associated with decreased local progression (32% vs 46%, P = .03) and no increase in grade 3 to 4 toxicity, except for nausea.
  
  
  CONCLUSIONS
  In this open-label, randomized trial involving patients with locally advanced pancreatic cancer with disease controlled after 4 months of induction chemotherapy, there was no significant difference in overall survival with chemoradiotherapy compared with chemotherapy alone and there was no significant difference in overall survival with gemcitabine compared with gemcitabine plus erlotinib used as maintenance therapy.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00634725.
authors.affiliation: Department of Digestive Oncology, Beaujon Hospital (AP-HP), Clichy, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Hammel
authors.affiliation: Department of Radiotherapy, Tenon Hospital (AP-HP), Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Huguet
authors.affiliation: Department of Gastroenterology, Erasme University Hospital, Brussels, Belgium.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: van Laethem
authors.affiliation: Department of Medical Oncology, Prince of Wales Hospital, Sydney, Australia5Australasian Gastrointestinal Trials Group (AGITG), Camperdown, Australia6Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Goldstein
authors.affiliation: Department of Radiology, Oncology, and Radiation Science, University of Uppsala, Uppsala, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Glimelius
authors.affiliation: Department of Gastroenterology, Jean Mermoz Hospital, Lyon, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Artru
authors.affiliation: Department of Gastroenterology, Saint-Luc University Clinics, Brussels, Belgium.
authors.forename: Ivan
authors.initials: I
authors.lastname: Borbath
authors.affiliation: Department of Gastroenterology, Robert Debré Hospital, Reims, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bouché
authors.affiliation: Australasian Gastrointestinal Trials Group (AGITG), Camperdown, Australia6Prince of Wales Clinical School, University of New South Wales, Sydney, Australia11Department of Medical Oncology, Nepean Hospital NSW, Sydney, Australia.
authors.forename: Jenny
authors.initials: J
authors.lastname: Shannon
authors.affiliation: Department of Medical Oncology, Saint-Antoine Hospital (AP-HP), Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: André
authors.affiliation: Department of Radiotherapy and Medical Oncology, Sainte-Catherine Institute, Avignon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Mineur
authors.affiliation: Department of Medical Oncology, Franco-British Hospital Institute, Levallois-Perret, France15Oncology Multidisciplinary Research Group (GERCOR), Paris, France.
authors.forename: Benoist
authors.initials: B
authors.lastname: Chibaudel
authors.affiliation: Department of Methodology and Quality of Life in Oncology, Hospital Minjoz, Besançon, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Bonnetain
authors.affiliation: Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Louvet
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D059248:Chemoradiotherapy; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018450:Disease Progression; D018572:Disease-Free Survival; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D003841:Deoxycytidine; D000069347:Erlotinib Hydrochloride; D000093542:Gemcitabine