Background: B2222 was the first large trial to show that 1st-line IM induces high objective response rates and durable disease control in pts with advanced GIST. Sequential study extensions allowed for ongoing IM treatment and extended pt follow-up, enabling evaluation of long-term survival and potential markers of disease control. Methods: Pts with advanced KIT⁺ GIST were enrolled in an open-label, multicenter trial and randomized 1:1 to receive 400 or 600 mg/d IM. The original 3-yr study was serially extended to treat pts, who continued IM for >10 yrs, and to monitor long-term overall survival (OS) and progression-free (TTP) rates. Results: Of 147 pts initially enrolled between July 2000 and April 2001, 56 continued IM therapy beyond 3 yrs. Maximum follow-up time for this analysis was 9.9 yrs (median 9.4 yrs). As of May 26, 2010, 26 pts (17.7%) remained on continuous IM since study entry; the GIST genotypes were: KIT exon 11 mutant (m), n=16; KIT exon 9 m, n=3; PDGFRA m, n=1; wild type, n=1; and unknown, n=5. Twenty-one of 30 pts (70%) withdrew during extensions, due to GIST progression (PD). The estimated TTP rate at 9 yrs for all 147 pts was 14%; this was similar for pts with complete or partial response (CR/PR, 16%) or stable disease (SD, 17%) as best overall response. The estimated 9-yr OS rate for all pts was 35%: 38% for those with CR/PR; 49% for SD; 0% for PD. Estimated 9-yr TTP rates by tumor bulk at baseline according to quartiles were: 29% in group 1 (<39.1 mm²), 11% in group 2 (39.1 – <102.1 mm²), 13% in group 3 (102.1 – <262.6 mm²), and 3% in group 4 (≥262.6 mm²). Of the pts who entered the extension study, 53.6%, 23.1%, 11.5%, and 11.5% from groups 1 to 4, respectively, remain on study. Estimated 9-yr OS rates by tumor bulk were 58%, 40%, 20%, and 23% in the 4 groups, respectively. Although safety was not captured systematically beyond 3 yrs, no unexpected long-term toxicities were observed, and IM remained well tolerated. Conclusions: A meaningful subset of pts with advanced GIST survived ≥9 yrs with 1st-line IM therapy. Pts with SD or CR/PR showed similar estimated 9-yr OS and TTP rates. Low tumor bulk at baseline predicted for longer TTP and improved OS.