Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors (GIST): A meta-analyis based on 1,640 patients (pts)

Abstract

10004 Background: The MetaGIST project aims to further explore the data of the two randomized studies comparing two doses of imatinib (400 mg od vs bid) for the treatment of GIST: EORTC/ISG/AGITG 62005 (EU-AUS) and SWOG/CALGB/NCI-C/ECOG/ICAS S0033 (US-CDN). Methods: End-points were progression free (PFS) and overall survival (OS). Investigated cofactors included age, sex, performance status (PS), primary tumor site, time from diagnosis, prior therapies, baseline biology, and KIT / PDGFRa mutations for a subset of 772 pts (47%). The logrank test (stratified) and the Cox multivariate model with interaction terms were used for the analysis. Results: The median follow-up was 45 months. A small but significant PFS advantage was documented for the high dose arm, consistently in both studies. OS was identical in the two arms (see table ). Males and pts with a poor PS, GIST from bowel origin, baseline low hemoglobin and high neutrophils counts (ANC) had a significant worse PFS (multivariate analysis); these factors are consistent between studies. In pts analyzed for mutations, wild type pts (HR=1.56), KIT exon 9 mutants (HR=2.17) and pts with other mutations (HR=2.56) had a worse prognosis than KIT exon 11 mutants (univariate analysis); all 3 factors remained in the multivariate model. The US-CDN study included significantly (P<0.01) more females, more GIST from bowel or stomach origin, less KIT exon 9 mutants and pts with a lower baseline ANC. In KIT exon 9 mutants, the PFS advantage with high dose imatinib previously reported in the EU- AUS study was not confirmed in the US-CDN dataset, but remains significant in the pooled dataset. The interaction between dose effect on PFS and prognostic factors was siginficant for KIT exon 9 mutations but not for other factors. Conclusions: This analysis confirms a small PFS advantage of high dose imatinib, essentially amongst KIT exon 9 mutants, but no OS advantage. Heterogeneity between the two studies is being further explored. [Table: see text] [Table: see text]