Results from a continuation trial of SU11248 in patients (pts) with imatinib (IM)-resistant gastrointestinal stromal tumor (GIST).

9011 Background: Resistance to IM eventually develops in most pts with metastatic GIST and is often correlated with secondary mutations in the genes encoding KIT or platelet-derived growth factor receptor alpha (PDGFRA) tyrosine kinases. SU11248 is an oral multi-targeted tyrosine kinase inhibitor with both anti-angiogenic and direct anti-proliferative activity mediated by signal blockade of several kinases, including VEGFR2, KIT, PDGFRA, and FLT3. SU11248 can overcome IM resistance in GIST caused by diverse genomic alterations (Demetri et al. Proc ASCO 2004; abstr 3001). We report longer term clinical results of a continuation study accruing pts treated in a prior phase I/II study.,From 07/02 to 07/04, 97 pts with GIST resistant to or intolerant of IM were enrolled in a phase I/II study and received one of three schedules of SU11248 administered by daily oral dosing with intermittent dosing breaks. The phase II schedule chosen was 50 mg/d daily for 4 weeks with a 2 week break. After 6 months on the phase I/II study, pts with continued clinical benefit from SU11248 were allowed to enter a continuation protocol in which tumor progression and safety were assessed.,32 GIST pts with continued clinical benefit (PR or stable disease > 6 months) have enrolled on the continuation protocol. As of 12/04, with median treatment time over 1 year, 26 pts remain on study, while 6 pts developed progressive disease. For 22 patients with RECIST-evaluable disease neither median time to progression nor overall survival has been reached. Grade 3 and 4 adverse events for this cohort of patients included: hypertension (16%), asymptomatic lipase elevation (15%), neutropenia (14%), fatigue (11%).,SU11248 shows promising clinical activity in pts with IM-resistant GIST and provides durable benefit in a selected population of pts. Molecular analyses of tumor genotype are in progress to understand this subset in more detail. [Table: see text].