TY - JOUR
T1 - One vs Three Years of Adjuvant Imatinib for Operable Gastrointestinal Stromal Tumor
T2 - A Randomized Trial
AU - Joensuu, Heikki
AU - Eriksson, Mikael
AU - Hall, Kirsten Sundby
AU - Hartmann, Joerg T.
AU - Pink, Daniel
AU - Schuette, Jochen
AU - Ramadori, Giuliano
AU - Hohenberger, Peter
AU - Duyster, Justus
AU - Al-Batran, Salah-Eddin
AU - Schlemmer, Marcus
AU - Bauer, Sebastian
AU - Wardelmann, Eva
AU - Sarlomo-Rikala, Maarit
AU - Nilsson, Bengt
AU - Sihto, Harri
AU - Monge, Odd R.
AU - Bono, Petri
AU - Kallio, Raija
AU - Vehtari, Aki
AU - Leinonen, Mika
AU - Alvegård, Thor
AU - Reichardt, Peter
PY - 2012
Y1 - 2012
N2 - Context 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. Design, Setting, and Patients 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. Intervention Imatinib, 400 mg per day, orally for either 12 months or 36 months, started within 12 weeks of surgery. Main Outcome Measures 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. Conclusion 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.
AB - Context 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. Design, Setting, and Patients 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. Intervention Imatinib, 400 mg per day, orally for either 12 months or 36 months, started within 12 weeks of surgery. Main Outcome Measures 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. Conclusion 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.
U2 - 10.1001/jama.2012.347
DO - 10.1001/jama.2012.347
M3 - Article
C2 - 22453568
VL - 307
SP - 1265
EP - 1272
JO - JAMA: The Journal of the American Medical Association
JF - JAMA: The Journal of the American Medical Association
SN - 0098-7484
IS - 12
ER -