title: One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial.
abstract: BACKGROUND
  Adjuvant imatinib administered for 12 months after surgery has improved recurrence-free survival (RFS) of patients with operable gastrointestinal stromal tumor (GIST) compared with placebo.
  
  
  OBJECTIVE
  To investigate the role of imatinib administration duration as adjuvant treatment of patients who have a high estimated risk for GIST recurrence after surgery.
  
  
  METHODS
  Patients with KIT-positive GIST removed at surgery were entered between February 2004 and September 2008 to this randomized, open-label phase 3 study conducted in 24 hospitals in Finland, Germany, Norway, and Sweden. The risk of GIST recurrence was estimated using the modified National Institutes of Health Consensus Criteria.
  
  
  METHODS
  Imatinib, 400 mg per day, orally for either 12 months or 36 months, started within 12 weeks of surgery.
  
  
  METHODS
  The primary end point was RFS; the secondary end points included overall survival and treatment safety.
  
  
  RESULTS
  Two hundred patients were allocated to each group. The median follow-up time after randomization was 54 months in December 2010. Diagnosis of GIST was confirmed in 382 of 397 patients (96%) in the intention-to-treat population at a central pathology review. KIT or PDGFRA mutation was detected in 333 of 366 tumors (91%) available for testing. Patients assigned for 36 months of imatinib had longer RFS compared with those assigned for 12 months (hazard ratio [HR], 0.46; 95% CI, 0.32-0.65; P < .001; 5-year RFS, 65.6% vs 47.9%, respectively) and longer overall survival (HR, 0.45; 95% CI, 0.22-0.89; P = .02; 5-year survival, 92.0% vs 81.7%). Imatinib was generally well tolerated, but 12.6% and 25.8% of patients assigned to the 12- and 36-month groups, respectively, discontinued imatinib for a reason other than GIST recurrence.
  
  
  CONCLUSIONS
  Compared with 12 months of adjuvant imatinib, 36 months of imatinib improved RFS and overall survival of GIST patients with a high risk of GIST recurrence.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00116935.
authors.affiliation: Department of Oncology, Helsinki University Central Hospital, Haartmaninkatu 4, PO Box 180, FIN-00029 Helsinki, Finland. heikki.joensuu@hus.fi
authors.forename: Heikki
authors.initials: H
authors.lastname: Joensuu
authors.forename: Mikael
authors.initials: M
authors.lastname: Eriksson
authors.forename: Kirsten
authors.initials: K
authors.lastname: Sundby Hall
authors.forename: Jörg T
authors.initials: JT
authors.lastname: Hartmann
authors.forename: Daniel
authors.initials: D
authors.lastname: Pink
authors.forename: Jochen
authors.initials: J
authors.lastname: Schütte
authors.forename: Giuliano
authors.initials: G
authors.lastname: Ramadori
authors.forename: Peter
authors.initials: P
authors.lastname: Hohenberger
authors.forename: Justus
authors.initials: J
authors.lastname: Duyster
authors.forename: Salah-Eddin
authors.initials: SE
authors.lastname: Al-Batran
authors.forename: Marcus
authors.initials: M
authors.lastname: Schlemmer
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bauer
authors.forename: Eva
authors.initials: E
authors.lastname: Wardelmann
authors.forename: Maarit
authors.initials: M
authors.lastname: Sarlomo-Rikala
authors.forename: Bengt
authors.initials: B
authors.lastname: Nilsson
authors.forename: Harri
authors.initials: H
authors.lastname: Sihto
authors.forename: Odd R
authors.initials: OR
authors.lastname: Monge
authors.forename: Petri
authors.initials: P
authors.lastname: Bono
authors.forename: Raija
authors.initials: R
authors.lastname: Kallio
authors.forename: Aki
authors.initials: A
authors.lastname: Vehtari
authors.forename: Mika
authors.initials: M
authors.lastname: Leinonen
authors.forename: Thor
authors.initials: T
authors.lastname: Alvegård
authors.forename: Peter
authors.initials: P
authors.lastname: Reichardt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001549:Benzamides; D017024:Chemotherapy, Adjuvant; D004334:Drug Administration Schedule; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha