9513 Background: Sunitinib malate (previously known as SU11248) is an oral multitargeted tyrosine kinase inhibitor with both antitumor and antiangiogenic effects due to blockade of KIT, PDGFRs, VEGFRs, FLT3, and RET. Initial results from this phase III trial showed sunitinib was associated with significantly longer TTP than placebo in IM-resistant GIST pts. Methods: This double-blind, placebo-controlled, phase III trial compared sunitinib 50 mg/day (N=207) to placebo (N=105) in IM-resistant or -intolerant GIST pts. Treatment was administered in 6-week cycles (4 weeks on, 2 weeks off treatment). The primary endpoint was TTP. Secondary endpoints included PFS, OS, ORR, and pain and health status (HS) measures. Pain relief response rate (PRRR) was defined as the proportion of pts who had ≥1 pain relief response event (based on weekly changes in present pain index of MPQ and analgesic consumption). HS was measured using the EQ-5D questionnaire. Results: A planned interim analysis showed significantly longer median TTP with sunitinib versus placebo (27.3 vs 6.4 weeks; HR, 0.33; P<0.001), which led to unblinding of the study and crossover of all placebo pts to open-label sunitinib. OS was also significantly longer with sunitinib (median OS will be presented). Sunitinib therapy induced PRs in 14 pts (6.8%) and durable SD (≥22 weeks) in 36 (17.4%) vs. 0% PR and SD ≥22 weeks in 2 (1.9%) pts on placebo. Four of 9 IM-intolerant pts achieved PR with sunitinib therapy versus 0 of 4 IM-intolerant pts treated with placebo. There was a trend for higher PRRR with sunitinib versus placebo in the ITT population (17.4% vs 9.5%, P=0.064) and in 174 pts who reported pain or analgesic use at baseline (31.0% vs 17.2%, P=0.052). The most common treatment-related AEs were fatigue, diarrhea, skin discoloration, and nausea, which were usually grade 1/2 and easily managed. Updated survival and tumor-control efficacy measures, tolerability, and HS results will be available for presentation. Conclusions: Sunitinib significantly prolonged TTP and OS in GIST pts for whom IM therapy had failed due to resistance or intolerance. This trial demonstrated major clinical benefit from a multitargeted tyrosine kinase inhibitor in pts resistant to a different kinase inhibitor. [Table: see text]
Effects of Fostamatinib, an Oral Spleen Tyrosine Kinase Inhibitor, in Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate: Results From a Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study
