TY - JOUR
T1 - Relationship between imatinib trough concentration and outcomes in the treatment of advanced gastrointestinal stromal tumours in a real-life setting
AU - Bouchet, Stéphane
AU - Poulette, Sylvie
AU - Titier, Karine
AU - Moore, Nicholas
AU - Lassalle, Régis
AU - Abouelfath, Abdelilah
AU - Italiano, Antoine
AU - Chevreau, Christine
AU - Bompas, Emmanuelle
AU - Collard, Olivier
AU - Duffaud, Florence
AU - Rios, Maria
AU - Cupissol, Didier
AU - Adenis, Antoine
AU - Ray-Coquard, Isabelle
AU - Bouché, Olivier
AU - Le Cesne, Axel
AU - Bui, Binh
AU - Blay, Jean Yves
AU - Molimard, Mathieu
N1 - Publisher Copyright:
© 2016 Elsevier Ltd. All rights reserved.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - Background Imatinib has dramatically improved the prognosis of advanced gastrointestinal stromal tumours (GISTs). Clinical trial data showed that patients with trough imatinib plasma concentrations (Cmin) below 1100 ng/ml (quartile 1) had shorter time to progression, but no threshold has been defined. The main objective of this study was to investigate in advanced GIST whether a Cmin threshold value associated with a longer progression-free survival (PFS) could be specified. This would be the first step leading to therapeutic drug monitoring of imatinib in GIST. Patients and methods Advanced GIST patients (n = 96) treated with imatinib 400 mg/d (41 stomach, 34 small bowel, and 21 other primary site localisations) were prospectively included in this real-life setting study. Routine plasma level testing imatinib (Cmin) and clinical data of were recorded prospectively. Results Small bowel localisation was associated with an increased relative risk of progression of 3.09 versus stomach localisation (p = 0.0255). Mean Cmin (±standard deviation) was 868 (±536) ng/ml with 75% inter-individual and 26% intra-patient variability. A Cmin threshold of 760 ng/ml defined by log-rank test was associated with longer PFS for the whole population (p = 0.0256) and for both stomach (p = 0.043) and small bowel (p = 0.049) localisations when analysed separately. Multivariate Cox regression analysis found that Cmin above 760 ng/ml was associated with 65% reduction risk of progression (p = 0.0271) in the whole population independently of the anatomical localisation. Conclusion Concentration of imatinib significantly influences duration of tumour control treatment in GIST patients with a Cmin threshold of 760 ng/ml associated with prolonged PFS in real-life setting.
AB - Background Imatinib has dramatically improved the prognosis of advanced gastrointestinal stromal tumours (GISTs). Clinical trial data showed that patients with trough imatinib plasma concentrations (Cmin) below 1100 ng/ml (quartile 1) had shorter time to progression, but no threshold has been defined. The main objective of this study was to investigate in advanced GIST whether a Cmin threshold value associated with a longer progression-free survival (PFS) could be specified. This would be the first step leading to therapeutic drug monitoring of imatinib in GIST. Patients and methods Advanced GIST patients (n = 96) treated with imatinib 400 mg/d (41 stomach, 34 small bowel, and 21 other primary site localisations) were prospectively included in this real-life setting study. Routine plasma level testing imatinib (Cmin) and clinical data of were recorded prospectively. Results Small bowel localisation was associated with an increased relative risk of progression of 3.09 versus stomach localisation (p = 0.0255). Mean Cmin (±standard deviation) was 868 (±536) ng/ml with 75% inter-individual and 26% intra-patient variability. A Cmin threshold of 760 ng/ml defined by log-rank test was associated with longer PFS for the whole population (p = 0.0256) and for both stomach (p = 0.043) and small bowel (p = 0.049) localisations when analysed separately. Multivariate Cox regression analysis found that Cmin above 760 ng/ml was associated with 65% reduction risk of progression (p = 0.0271) in the whole population independently of the anatomical localisation. Conclusion Concentration of imatinib significantly influences duration of tumour control treatment in GIST patients with a Cmin threshold of 760 ng/ml associated with prolonged PFS in real-life setting.
KW - Gastrointestinal stromal tumour
KW - Imatinib
KW - Therapeutic drug monitoring
UR - http://www.scopus.com/inward/record.url?scp=84957537996&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2015.12.029
DO - 10.1016/j.ejca.2015.12.029
M3 - Article
C2 - 26851399
AN - SCOPUS:84957537996
SN - 0959-8049
VL - 57
SP - 31
EP - 38
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -