Evaluation of imatinib mesylate (IM) in patients with large volume gastrointestinal stromal tumors (GISTs)

Abstract

10054 Background: GIST size is one of the most important prognostic markers for recurrence and poor survival. However, little information exists regarding the relationship between tumor volume and clinical outcome after treatment with IM. A phase II randomized clinical trial of two dose levels of IM (400 vs. 600 mg daily) in pts with incurable GIST was previously presented (Proc ASCO 2001; Combined GI Symp 2004 and 2007). With median follow-up of 64 months, we report additional analyses of the relationship between tumor volume and IM efficacy. Methods: Data on initial tumor bulk were prospectively collected, and 146 pts were separated into quartiles according to total tumor volume: < 39.1 cm2 (n=36), 39.1 = 102.16 cm2 (n=37), 102.16 = 262.6 cm2 (n=36), = 262.6 cm2 (n=37). Tumor bulk was correlated with standard efficacy outcomes. Results: The overall response rate (CR + PR) for all pts was 68.1% (95% CI 59.8% - 75.5%). Median time-to-progression (TTP) was 24 months, and overall survival (OS) was 57 months. The overall response rates for the four quartiles according to tumor burden (lowest to highest) were: 64%, 70%, 75%, and 65% respectively. Median TTP by quartile was: 57, 25, 18, and 17 months. Median OS for these same groups: not reached, 57, 47, and 35 months. The Kaplan-Meier estimates of patients alive at 64 months based on tumor bulk were 62%, 40%, 44%, and 31% respectively. Disease bulk was an independent prognostic factor for overall survival using a Cox regression model including sex, performance status, IM dose, gender, age, prior chemotherapy, and tumor volume, but not when baseline hemoglobin was included. Conclusions: Pts with bulky GISTs progress sooner and die more quickly than those with lesser tumor volumes, though other factors may contribute as well. Even pts with the bulkiest tumors frequently respond to treatment with IM, however. TTP for this population approaches 1.5 yrs, and median survival for these pts approximates 3 yrs. One-third of pts with extraordinarily bulky GISTs are long-term survivors. The potential relationship between baseline hemoglobin and tumor bulk requires further investigation. [Table: see text]