Who Are The Long Responders To Imatinib (Im) In Patients With Advanced Gist? Results Of The Bfr14 Prospective French Sarcoma Group Randomized Phase Iii Trial.

10048 Background: The aim of this work was to characterize patient (pts) characteristics and the mutational status of GIST who benefit the most from IM in term of prolonged response and overall survival. Methods: Among the 434 pts included between June 2002 to July 2009 in the prospective multicentric BFR14 trial, we selected the 236 pts having started IM 400 mg daily for at least 5 years (pts enrolled before January 2006). Pts who have no exhibited any kind of progression have been retrospectively analyzed both clinically and biologically. KIT and PDGFR mutations were analyzed using DHPLC and direct sequencing of frequently mutated exons (KIT 9, 11, 13, 14, 18, PDGFR 12, 14, 18). Characteristics data were compared between pts with or without progression. Results: As of January 2011, 197/236 selected pts have progressed or died since IM initiation and 39 pts are still free of progression. The characteristics of these long term survivors favorable cohort of pts are as following: a non significant increase of gastric GIST (48.7% vs 29.7%), PS 0 (P=0.04) and a small tumor volume at inclusion (median 49 mm vs 102) (p=0.003). As of now, 27 out 39 prolonged responding pts to IM are evaluable for mutational analysis. All but three pts (2 with exon 9 and 1 WT) pts harbored an exon 11 mutation. The most common genetic alteration (16 out 24 pts) affects codons 557 and/or 558. Conclusions: Pts in good performance status with a small tumor volume at inclusion and harboring an exon 11 mutation in the vicinity of codon 557-558 confere to pts a high sensibility to IM and predict a prolonged outcome.