Surgery of residual disease following imatinib mesylate in advanced gastrointestinal stromal tumors (GIST)

Abstract

9038 Background: To retrospectively analyze the outcome of advanced GIST patients undergoing surgery of residual disease after a period of Imatinib mesylate therapy. Methods: We reviewed patients with advanced GIST who received Imatinib mesylate within a EORTC-STBSG led intergroup trial, or within a Southern European Phase II study, or as a standard of care, and were subsequently operated on at the Istituto Nazionale Tumori, Milano, Italy, between July 2002 and September 2004. Group A patients were operated on while in response; Group B patients after primary or secondary progression. A total of 25 patients were identified, with a median follow-up of 18 months. Median duration of Imatinib therapy before surgery was 17 months. Mutational status is presently available for 14 patients (48%). Results: In Group A patients (n = 19), all were found to have remnants in the abdominal cavity/liver, with a variable proportion of viable cells at pathologic examination, irrespective of radiologic PR or CR. All biomolecularly assessed patients carried an exon 11 mutation (1 patient along with a coexisting acquired exon 13 mutation), except one wild-type. After a median follow up of 19.9 months, all patients are alive, 16 patients (84%) with no evidence of progression (all continued Imatinib after surgery), while 3 patients failed at 16–18 months (2 of them had discontinuated Imatinib). In Group B (n = 6), all patients had viable disease at pathologic examination. Amongst assessed patients, 25% showed an exon 9 mutation, and 75% an exon 11 mutation (1 patient with an acquired concomitant exon 14 mutation). All patients failed after a median of 6 months, 4 are alive and 2 died of disease at 3 and 10 months after surgery. Conclusions: Also this series suggests not to discontinuate Imatinib therapy after surgery of residual disease, even if complete. The prognostic advantage from surgery of residual disease in response is left to elucidate by combining available series. On the other hand, patients with progressive disease are candidates for second-line molecular-targeted therapies, surgery being likely of minimal benefit. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis