10015 Background: We previously demonstrated that interruption of IM treatment after 1, 3, and 5 yrs in responding patients (pts) with advanced GIST are associated with rapid relapse. The impact of IM interruption on secondary resistance and overall survival (OS) with longer-term follow-up was unclear. METHODS This prospective multicenter BFR14 study was initiated in June 2002 and closed for accrual in July 2009. Pts with GIST free of progression after 1, 3 or 5 yrs of IM 400 mg/day were randomly assigned to continue (C arm) or interrupt (I arm) IM. Reintroduction of IM (same dose) upon progression was allowed for pts in the I group. Primary endpoint was Progression Free Survival (PFS). Secondary endpoints included OS and time to secondary resistance (TSR) defined as time to progression under IM treatment (i.e. first progression in the C arm and progression after reintroduction of IM in the I arm). RESULTS As of January 2011, 434 pts were included in this trial. Fifty-eight, 50 and 27 non progressive pts at 1, 3 and 5 yrs were randomized and median follow-up from randomization were 74, 47 and 18 months, respectively. Results are summarized in the table. PFS was significantly lower in the I arms than in C arms. IM reintroduction allowed tumor control in 94% (49/52) of pts. The rates of pts with relapse at 2 yrs post-randomisation decreases with the duration of treatment: 38%, 20% and 0% of pts randomised after 1, 3 and 5 yrs of IM treatment in the C arm. No difference for TSR or OS is observed between the 2 arms. CONCLUSIONS Reintroduction of IM allowed tumor control in almost all pts. IM interruption had no impact on TSR The rate of secondary resistance decreases with longer duration of IM treatment. [Table: see text].