New paradigms in gastrointestinal stromal tumour management.

BACKGROUND

Targeted agents have improved the prognosis for patients with advanced gastrointestinal stromal tumours (GISTs). Many patients exhibit intolerance or resistance to first-line therapy with imatinib mesylate. Sunitinib malate is approved multinationally for the treatment of advanced imatinib-refractory GIST.

DESIGN

This article reviews responses to imatinib and sunitinib reported in clinical trials in advanced GIST and discusses the effect of mutational status on treatment responses; therapeutic developments in GIST treatment are also reviewed.

RESULTS

Imatinib 400 mg/day has shown efficacy for first-line treatment of advanced GIST, particularly in patients with KIT exon 11 mutations. Sunitinib 50 mg/day (Schedule 4/2) has demonstrated effectiveness and tolerability in imatinib-refractory GIST, including patients who would be excluded from clinical trials. Sunitinib is associated with longer median overall survival in patients with primary KIT exon 9 mutations and wild-type GIST compared with KIT exon 11 mutations in a retrospective study. Ongoing studies, including imatinib in the adjuvant setting and the use of targeted agents in sequence or in combination, will further refine the therapeutic pathway for advanced GIST.

CONCLUSIONS

The availability of targeted therapies and greater knowledge of the effect of mutational status on patient responses will assist in optimising outcomes in advanced GIST.