Subpopulation analyses in a worldwide treatment-use trial of sunitinib (SU) in GIST patients (pts) with resistance or intolerance to prior imatinib (IM) therapy

Abstract

10022 Background: SU is an oral, multitargeted TKI of KIT, PDGFRs, VEGFRs, RET and FLT3, approved multinationally for the treatment of IM-resistant/-intolerant GIST. The aims of this study are to provide access to SU to GIST pts who were ineligible for SU clinical trials or for whom SU is unavailable prior to regulatory approval in their country, and to collect safety/efficacy data in a large number of GIST pts. Methods: In this ongoing open-label study, pts with advanced GIST and prior IM failure receive SU at a starting dose of 50 mg/d in 6-wk cycles (4 wks on treatment, 2 wks off). Assessments include safety/tolerability measures, response (per local standard of care) and OS. Because of the variability of response evaluations, treatment duration (TD; time from first dose to the earlier of termination date or 2 wks after last dose) was analyzed as a surrogate efficacy measure. Results: As of March 1, 2006, 768 pts enrolled at 96 centers in 33 countries had received =1 dose of SU (ITT population). Of these, 362 had discontinued treatment (lack of efficacy: 25%; AE: 12%). Median TD (ITT population) was 126 d (range: 1–618); 55% of pts had received =3 mos of treatment; 32%, =6 mos and 16%, =9 mos. Median TD was similar for pts irrespective of tumor histological subtype (epithelioid: 125 d, n=85; spindle cell: 127 d, n=414; mixed: 126 d, n=100; other subtypes: 114 d, n=158; P=0.17). Median TD was longer in pts with ECOG PS 0/1 (127 d, n=637) vs 2 (84 d, n=96; P<0.0001) and pts aged <65 (127d, n=486) vs =65 yrs (97d, n=281; P=0.011). Median OS has not been reached. The impact of baseline factors on survival will be presented. The most common AEs of any cause were fatigue (42%), diarrhea (38%) and nausea (32%), which were usually grade 1/2. The most common grade =3 AEs of any cause were abdominal pain (4%), vomiting (3%) and dehydration (2%). 3% of pts have demonstrated hypothyroidism. Hematologic AEs (total, grade 3/4) included anemia (56%, 5%), thrombocytopenia (35%, 5%) and neutropenia (22%, 10%). Conclusions: In this ongoing study of a large, relatively heterogeneous population of IM-resistant/-intolerant GIST pts, SU demonstrated acceptable tolerability and clinical efficacy that is highly consistent with prior studies. No significant financial relationships to disclose.