TY - JOUR
T1 - Discontinuation of imatinib in patients with advanced gastrointestinal stromal tumours after 3 years of treatment
T2 - An open-label multicentre randomised phase 3 trial
AU - Le Cesne, Axel
AU - Ray-Coquard, Isabelle
AU - Bui, Binh Nguyen
AU - Adenis, Antoine
AU - Rios, Maria
AU - Bertucci, François
AU - Duffaud, Florence
AU - Chevreau, Christine
AU - Cupissol, Didier
AU - Cioffi, Angela
AU - Emile, Jean François
AU - Chabaud, Sylvie
AU - Pérol, David
AU - Blay, Jean Yves
N1 - Funding Information:
ALC has received honoraria from Pharmamar, Pfizer, and Novartis. J-YB has received honoraria from Novartis; has received consultancy fees from GlaxoSmithKline, Novartis, Pfizer, Pharmamar, and Roche; has received payment for lectures from Novartis, Pfizer, and Roche; and has received payment for the preparation of a manuscript by Novartis. J-YB's institution has received a grant from Novartis, Pfizer, Pharmamar, and Roche. All other authors declared no conflicts of interest.
PY - 2010/10/1
Y1 - 2010/10/1
N2 - Background: The effect of imatinib discontinuation on progression-free survival and overall survival in long-lasting responders with advanced gastrointestinal stromal tumours (GIST) is unknown. We assessed treatment interruption in patients with non-progressive disease according to the Response Evaluation Criteria In Solid Tumors criteria after 3 years of imatinib in a randomised trial. Methods: In this open-label national multicentre phase 3 study in France, patients with GIST free of progression after 3 years of imatinib 400 mg/day were randomly assigned to continue or interrupt imatinib. Randomisation was done centrally and independently from other study procedures with computer-generated permuted blocks of two and four patients stratified by participating centre and presence or absence of residual disease on CT scan. The primary endpoint was progression-free survival. An interim analysis was planned after the first 50 randomly assigned patients. Analysis was done according to the intention-to-treat principle-ie, all patients randomly assigned to a study group were included. This study is registered with ClinicalTrial.gov, number NCT00367861. Findings: 434 patients were enrolled in this trial between May 27, 2002, and May 5, 2009. Between June 13, 2005, and May 30, 2007, 50 patients with non-progressive disease who had received 3 years of treatment with imatinib were randomly assigned to continue or interrupt their treatment, 25 patients in each group. By Dec 7, 2009, after a median follow-up of 35 months (95% CI 33-38) after random assignment, 2-year progression-free survival was 80% (95% CI 58-91) in the continuation group and 16% (5-33) in the interruption group (p<0·0001). There was no difference in adverse events grade 3 or greater (oedema and asthenia) between the two groups. Interpretation: Imatinib interruption after 3 years in responders results in a high risk of rapid progression in patients with advanced GIST. Discontinuation of imatinib is not recommended outside clinical trials unless patients experience significant toxic effects. Funding: Conticanet, the Ligue Contre Le Cancer du Rhone, and Novartis.
AB - Background: The effect of imatinib discontinuation on progression-free survival and overall survival in long-lasting responders with advanced gastrointestinal stromal tumours (GIST) is unknown. We assessed treatment interruption in patients with non-progressive disease according to the Response Evaluation Criteria In Solid Tumors criteria after 3 years of imatinib in a randomised trial. Methods: In this open-label national multicentre phase 3 study in France, patients with GIST free of progression after 3 years of imatinib 400 mg/day were randomly assigned to continue or interrupt imatinib. Randomisation was done centrally and independently from other study procedures with computer-generated permuted blocks of two and four patients stratified by participating centre and presence or absence of residual disease on CT scan. The primary endpoint was progression-free survival. An interim analysis was planned after the first 50 randomly assigned patients. Analysis was done according to the intention-to-treat principle-ie, all patients randomly assigned to a study group were included. This study is registered with ClinicalTrial.gov, number NCT00367861. Findings: 434 patients were enrolled in this trial between May 27, 2002, and May 5, 2009. Between June 13, 2005, and May 30, 2007, 50 patients with non-progressive disease who had received 3 years of treatment with imatinib were randomly assigned to continue or interrupt their treatment, 25 patients in each group. By Dec 7, 2009, after a median follow-up of 35 months (95% CI 33-38) after random assignment, 2-year progression-free survival was 80% (95% CI 58-91) in the continuation group and 16% (5-33) in the interruption group (p<0·0001). There was no difference in adverse events grade 3 or greater (oedema and asthenia) between the two groups. Interpretation: Imatinib interruption after 3 years in responders results in a high risk of rapid progression in patients with advanced GIST. Discontinuation of imatinib is not recommended outside clinical trials unless patients experience significant toxic effects. Funding: Conticanet, the Ligue Contre Le Cancer du Rhone, and Novartis.
UR - http://www.scopus.com/inward/record.url?scp=77957341199&partnerID=8YFLogxK
U2 - 10.1016/S1470-2045(10)70222-9
DO - 10.1016/S1470-2045(10)70222-9
M3 - Article
C2 - 20864406
AN - SCOPUS:77957341199
SN - 1470-2045
VL - 11
SP - 942
EP - 949
JO - The Lancet Oncology
JF - The Lancet Oncology
IS - 10
ER -