Impact of mutational status and other prognostic factors on survival in patients with advanced GIST treated with standard-dose imatinib (IM): Results from the BFR14 phase III trial of the French Sarcoma Group.

Abstract

10548 Background: Factors predicting progression free survival (PFS) and overall survival (OS) of patients (pts) with advanced GIST treated with 400 mg daily dose IM were investigated. As mutational status was a secondary objective of the BFR14 study, we wanted to evaluate the added value of these genomic profiles to conventional clinical prognostic factors. Methods: 434 pts were included in this prospective multicenter trial from June 2002 to July 2009. Prognostic factors for survival were investigated in the cohort where the mutational status was available. A multivariate Cox model including baseline characteristics statistically significant in univariate were included in a backward procedure to identify independent prognostic factors for PFS then OS. Results: Mutational analysis were available in 322 pts. Material was insufficient in 55 cases (12.5%), incomplete results were obtained in 39 pts (9%). There were 196 KIT genetic alterations (exon 11: 173 pts, exon 9: 22 pts, exon 17: 1 pt), 6 GIST with a PDGFRA mutations and 26 GIST WT. The analysis of prognostic factors was performed in all mutated and non-mutated GIST (221 pts) except for pts with a KIT exon 17 and PDGFRa mutation. As of January 2013, median follow-up was 73 months (m) (CI95%:63; 86), 147 progressions (67%) were notified and 84 deaths (38%) occurred. The median PFS and OS were 12.3 m (CI95%: 2.1;32.7) and 54.9 m (CI95%:16.5;83.8) for WT GIST, 12.6m (CI95%: 6.1;30.8) and 55m (CI95%:33.5;83.0) for KIT exon 9 and 39.4m (CI95%: 31.4;54.4) and not reached for KIT exon 11, respectively. An initial low tumour volume, gender (female), and CD34 positivity were the three independent prognostic factors of a higher PFS. A higher OS was independently predicted by PS, low neutrophil counts, KIT exon 11 alterations, normal lymphocyte count, lower tumor size and female’s gender. Conclusions: GIST pts harboring a KIT exon 11 mutations have the better outcome but the mutational status is not the only prognostic factor influencing the outcome of pts. The clinical (gender, PS, tumor size) and biological characteristics (lymphocytes and neutrophil counts) remain critical for OS.