10059 Background: Blood pressure (BP) changes are significantly associated with use of SU. We describe systolic/diastolic BP (SBP/DBP) variations and clinically meaningful hypertension (CMH) using P-controlled data. Methods: A phase III trial randomized 361 pts with advanced GIST following failure of imatinib to blinded SU, 50 mg daily, (n=243) in cycles (cy) of 4/2 weeks on/off SU vs. P (n=118). The previously reported primary endpoint of the trial was time to tumor progression. Crossover resulted in higher exposure for pts randomized initially to SU (8.98 cy) vs. P (1.7 cy). To maintain comparability between groups, we restricted the analysis of BP variation to the first three cy of study. BP data were available on day 1 and 28 of each cy. Additionally we conducted a separate analysis with the entire data set, censoring for crossover pts, in order to assess CMH events defined as 1) an increase of at least 25 mmHg for SBP or 15 mmHg for DBP, or an increase of at least 10 mmHg to a level over 150 for SBP and 95 for DBP lasting >2 weeks or requiring change in antihypertensive or study medication, or 2) severe hypertension (SH: SBP ≥180 or DBP ≥120 mmHg with evidence of target organ dysfunction). Three cardiologists assisted by a medical oncologist, all blinded to treatment allocation, adjudicated SH events. Results: Data for both study arms during the first three cy are presented in the Table. For the second analysis, the incidence rates (IR: events per 100 patient-cy) of CMH for SU/P were 11.82/9.32 (HR: 2.1; 95% CI: 1.24-3.57). All 16 adjudicated SH were in SU, none were fatal, and two were in patients with normal baseline BP. Conclusions: These P-controlled data, albeit limited by differential exposure, allow for quantification of early BP changes during exposure to SU, demonstrating BP elevation with partial resolution when off SU. Nonfatal SH were seen in patients on SU, most of whom had pre-existing abnormal baseline BP. These data emphasize the need to monitor BP carefully before and during SU or other VEGFR- targeting treatment. SBP/DBP (mmHg) Cy-Day P SU 1-1 129.8/76.3 128/75.2 1-28 128.7/76.9 137.5/82.1 2-1 128.4/77.4 131.4/77.3 2-28 129.9/78.7 140.2/84.3 3-1 126.5/72.7 132.1/77.8 3-28 125.6/78.5 141.2/83.8 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Alnylam Pharmaceuticals, Amgen, ARIAD, Bayer, Genentech, Genentech/Roche, GlaxoSmithKline, Infinity, Johnson & Johnson, MethylGene Canada, Novartis, Pfizer, Roche Kolltan Pharmaceuticals, Pfizer, Plexxikon Novartis, Pfizer, Roche, sanofi-aventis Amgen, ARIAD, Bristol-Myers Squibb, Genentech/Roche, Infinity, Johnson & Johnson, Novartis, Pfizer, Roche, Synta Ariad, Infinity, Johnson & Johnson Pfizer