Phase II study of adjuvant imatinib mesylate (IM) in patients after resection of primary gastrointestinal stromal tumor (GIST): Efficacy and safety at one year.

Abstract

e20514 Background: The mainstay treatment of primary GIST is surgery, but GIST often recurs even after complete resection. This study assessed the safety and efficacy of adjuvant IM in patients (pts) with resected GIST at intermediate/high risk of tumor recurrence. Methods: This open-label, single arm, prospective Ph II study (NCT01172548) was conducted in Asia Pacific/Africa/Russia/Middle East/Europe in eligible pts: aged ≥18 years (yrs), having had complete gross resection of primary GIST within 70 days of enrollment, with CD117 +ve, WHO PS ≤1, and no other adjuvant therapy. The planned sample size was 150 pts. Pts were to receive IM (400 mg/day, po) for 2 yrs post surgery. Dose modifications were allowed for toxicity. The primary endpoint was recurrence-free survival (RFS) rate at 2 yrs (based on CT/MRI and survival) in ITT pts (all pts who received ≥1 dose of study drug); null hypothesis based on historic data controls treated with surgery alone: RFS rate at 2 yrs of 0.7 (1 yr rate 0.98) (NCT00041197). A protocol-planned analysis at 1 yr in all enrolled pts (mITT) included safety, RFS, and overall survival. The study was approved by IRB/IEC/REB; all pts provided written informed consent. Results: Pt accrual was complete with 127 pts in the mITT population. Most pts (n=94, 74%) were <65 yrs (median 56 [19–81] yrs); female (53%). Most common primary tumor sites: stomach (n=68, 54%), small intestine (n=48, 38%), colon/rectum (n=7, 6%). Main discontinuations (n=24, 18%): disease progression (n=8, 6%); withdrawal of consent (n=7, 5%); adverse events (AEs) and lost to follow-up (each n=3, 2%). Mean RFS rate at 1 yr was 0.95 (95% CI 0.907–0.993). Most AEs were mild or moderate (Table); no deaths occurred by 1 yr. Conclusions: Adjuvant IM 400 mg/day was efficacious and had a promising safety profile at 1 yr in pts after complete resection of primary GIST. [Table: see text]