1419P - Prospective analysis in GIST patients on the role of alpha-1 acid glycoprotein (AGP) in imatinib exposure

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics GIST
Presenter Sander Bins
Citation Annals of Oncology (2016) 27 (6): 483-492. 10.1093/annonc/mdw388
Authors S. Bins1, K. Eechoute2, J.S.L. Kloth2, F.M. de Man2, A. Oosten2, P. de Bruijn2, S. Sleijfer2, R. Mathijssen2
  • 1Medical Oncology, Erasmus MC Cancer Institute, 3015 CN - Rotterdam/NL
  • 2Medical Oncology, Erasmus MC Cancer Institute, Rotterdam/NL

Abstract

Background

For imatinib, a relationship between systemic exposure and clinical outcome has been suggested. Importantly, imatinib concentrations are not stable and decrease over time for which several mechanisms have been suggested. One theory assumes that reduction of the inflammatory syndrome, due to decreasing tumor burden or due to resolving surgery effects, leads to lower levels of the acute phase protein alpha-1 acid glycoprotein (AGP). Consequently, imatinib is proposed to be bound less to this protein, causing a larger proportion of the drug to be available for elimination, which in turn leads to lower systemic exposure over time. Here, we investigated if a decrease in AGP is the main cause of the decrease in imatinib exposure.

Methods

We prospectively measured imatinib trough concentrations (Cmin) in 31 patients with GIST, at 1, 3, and 12 months from start of imatinib treatment. At the same time points AGP was measured. Correlations were tested using Pearson's correlation coefficient and geometric means were compared using ANOVA. The study was approved by the local institutional review board (protocol number MEC13-203) and written informed consent was obtained from all individual participants included in the study.

Results

Overall, imatinib Cmin and AGP were correlated (r2 = 0.607; p 

Conclusions

We show that systemic AGP concentrations are not likely to be a key player in the decrease of systemic imatinib exposure over time. As long as the inter-individual changes in imatinib exposure remain unexplained, researchers should standardize the sampling times of imatinib in order to be able to compare the clinical applicability of TDM.

Clinical trial identification

Legal entity responsible for the study

Erasmus MC Cancer Institute

Funding

Erasmus MC Cancer Institute

Disclosure

All authors have declared no conflicts of interest.