Long-term follow-up of a phase II randomized trial in advanced gastrointestinal stromal tumor (GIST) patients (pts) treated with imatinib mesylate

Abstract

9528 Background: Imatinib achieves tumor control in most pts with advanced GIST, but the durability of remissions has not been well described. We now present an updated long-term analysis of a randomized phase II trial first presented in 2001, with a median follow-up of 52 months. Methods: 147 pts with unresectable or metastatic malignant GIST were randomized to treatment with daily dosing of imatinib, 400 or 600 mg po. Results: Two pts (1%) achieved a complete response, 98 (67%) achieved a partial response (PR), and 23 (16%) exhibited stable disease (SD) as their best response. Median time-to-response was 13 weeks (95% CI; 12–23 weeks), but one quarter of pts responded after 23 weeks. No significant response differences were seen between the two dose levels tested. The median duration of response was 27 months, and median overall survival was 58 months. Pts with SD or PR had similar 4-year survival rates (64% versus 62%). KIT and/or PDGFRA mutational analyses were obtained in 87% of patients, and the mutational status was highly significant in predicting outcome. GISTs harboring KIT mutations in exon 11, exon 9, and with no detectable mutations in KIT or PDGFRA demonstrated PR rates of 87%, 48%, and 0%, respectively. The median survival for pts with exon 11 KIT mutations has not yet been reached, and it was 45 months for those with exon 9 mutations. Conclusions: While late progression can be seen in GIST pts treated with imatinib, the majority of pts derive benefit. Survival in those achieving SD parallels those with PRs. Late responses are often seen in pts with initial SD, and responses in general are of lasting duration. In particular, pts with KIT mutations in exon 11 (the most common exon affected) have very high response rates and favorable long term survival. [Table: see text]