Imatinib

ACOSOG Z9001 (NCT00041197) was a phase III, double-blind, placebo-controlled trial of 713 patients with fully resected KIT-variant GISTs measuring at least 3 cm. Patients were randomly assigned to receive either imatinib 400 mg daily (n = 359) or placebo (n = 354) for 1 year after surgical resection.[4]

ACOSOG Z9001 (NCT00041197) was a phase III, double-blind, placebo-controlled trial of 713 patients with fully resected KIT-variant GISTs measuring at least 3 cm. Patients were randomly assigned to receive either imatinib 400 mg daily (n = 359) or placebo (n = 354) for 1 year after surgical resection.[4]

After a median follow-up of 19.7 months, disease recurrence or death occurred in 30 patients (8.4%) in the imatinib arm and 70 patients (19.8%) in the placebo arm.

ACOSOG Z9001 (NCT00041197) was a phase III, double-blind, placebo-controlled trial of 713 patients with fully resected KIT-variant GISTs measuring at least 3 cm. Patients were randomly assigned to receive either imatinib 400 mg daily (n = 359) or placebo (n = 354) for 1 year after surgical resection.[4]

The 1-year recurrence-free survival (RFS) rate was 98% in patients who received imatinib (95% confidence interval [CI], 96%–100%) and 83% (95% CI, 78%–88%) in patients who received placebo (hazard ratio [HR], 0.35; 95% CI, 0.22–0.53; P < .0001).[4][Level of evidence B1] No difference was noted in overall survival (OS) (HR, 0.66; 95% CI, 0.22–2.03; P = .4714).

ACOSOG Z9001 (NCT00041197) was a phase III, double-blind, placebo-controlled trial of 713 patients with fully resected KIT-variant GISTs measuring at least 3 cm. Patients were randomly assigned to receive either imatinib 400 mg daily (n = 359) or placebo (n = 354) for 1 year after surgical resection.[4]

Dose-reduction or interruption because of adverse events occurred in 14.5% of patients in the imatinib arm and 2.8% of patients in the placebo arm. Grade 3 or 4 events occurred in 30.9% of patients in the imatinib arm and 18.3% of patients in the placebo arm.

EORTC-62024 (NCT00103168) was a phase III open-label trial of 908 patients with fully resected (R0 or R1 margin) KIT-variant GISTs at intermediate or high risk of recurrence. Patients were randomly assigned to receive either imatinib 400 mg daily (n = 454) or observation (n = 454) for 2 years.[10]

EORTC-62024 (NCT00103168) was a phase III open-label trial of 908 patients with fully resected (R0 or R1 margin) KIT-variant GISTs at intermediate or high risk of recurrence. Patients were randomly assigned to receive either imatinib 400 mg daily (n = 454) or observation (n = 454) for 2 years.[10]

At a median follow-up of 4.7 years, RFS rates were improved for patients who received imatinib compared with patients who underwent observation at 3 years (84% vs. 66%) and 5 years (69% vs. 63%) (log-rank P < .001).[10][Level of evidence B1] The 5-year OS rate did not differ between the imatinib and observation arms (91.8% vs. 92.7%).

EORTC-62024 (NCT00103168) was a phase III open-label trial of 908 patients with fully resected (R0 or R1 margin) KIT-variant GISTs at intermediate or high risk of recurrence. Patients were randomly assigned to receive either imatinib 400 mg daily (n = 454) or observation (n = 454) for 2 years.[10]

The 5-year imatinib failure-free survival rate (day of randomization to the start of a new systemic treatment or death) was 87% in the imatinib arm and 84% in the observation arm (HR, 0.79; 98.5% CI, 0.50–1.25; P = .21).[10][Level of evidence B1]

EORTC-62024 (NCT00103168) was a phase III open-label trial of 908 patients with fully resected (R0 or R1 margin) KIT-variant GISTs at intermediate or high risk of recurrence. Patients were randomly assigned to receive either imatinib 400 mg daily (n = 454) or observation (n = 454) for 2 years.[10]

A final analysis at a median follow-up of 9.1 years showed RFS rates of 70% and 63% at 5 and 10 years, respectively, for patients in the imatinib arm, and rates of 63% and 61% at 5 and 10 years, respectively, for patients in the observation arm (HR, 0.71; 95% CI, 0.57–0.89; P = .002). There was no difference in OS between patients who received imatinib and patients who underwent observation (93% vs. 92% at 5 years, 80% vs. 78% at 10 years; HR, 0.88; 95% CI, 0.65–1.21; P = .43).[9][Levels of evidence B1 and A1]

SSG XVIII (NCT00116935) was a phase III open-label trial of 400 patients with fully resected, high-risk GISTs. Patients were randomly assigned to receive imatinib 400 mg daily for either 1 year (n = 200) or 3 years (n = 200) after resection.[5]

SSG XVIII (NCT00116935) was a phase III open-label trial of 400 patients with fully resected, high-risk GISTs. Patients were randomly assigned to receive imatinib 400 mg daily for either 1 year (n = 200) or 3 years (n = 200) after resection.[5]

After a median follow-up of 54 months, the RFS rate was 65.6% in the 3-year arm and 47.9% in the 1-year arm (HR, 0.46; 95% CI, 0.32–0.65; P < .001).[5][Level of evidence B1]

SSG XVIII (NCT00116935) was a phase III open-label trial of 400 patients with fully resected, high-risk GISTs. Patients were randomly assigned to receive imatinib 400 mg daily for either 1 year (n = 200) or 3 years (n = 200) after resection.[5]

The 5-year OS rate was 92% in the 3-year arm and 81.7% in the 1-year arm (HR, 0.45; 95% CI, 0.22–0.89; P = .02).[5]

SSG XVIII (NCT00116935) was a phase III open-label trial of 400 patients with fully resected, high-risk GISTs. Patients were randomly assigned to receive imatinib 400 mg daily for either 1 year (n = 200) or 3 years (n = 200) after resection.[5]

Although generally well-tolerated in both groups, grade 3 or 4 events occurred in 32.8% of patients in 3-year arm and 20.1% of patients in the 1-year arm. Treatment discontinuation occurred in 25.8% of patients in 3-year arm and 12.6% of patients in the 1-year arm.

SSG XVIII (NCT00116935) was a phase III open-label trial of 400 patients with fully resected, high-risk GISTs. Patients were randomly assigned to receive imatinib 400 mg daily for either 1 year (n = 200) or 3 years (n = 200) after resection.[5]

A post-hoc exploratory analysis suggested that patients with KIT exon 11–variant GISTs derived the most benefit from a longer duration of imatinib (5-year RFS, 71.0% vs. 41.3%; P < .001).[6]

PERSIST-5 (NCT00867113) was a single-arm phase II trial of 91 patients with fully resected, high-risk GISTs. Patients received imatinib (400 mg daily) for up to 5 years.[15][Level of evidence C1]

PERSIST-5 (NCT00867113) was a single-arm phase II trial of 91 patients with fully resected, high-risk GISTs. Patients received imatinib (400 mg daily) for up to 5 years.[15][Level of evidence C1]

The median treatment duration was 55.1 months, but with a large range (0.5–60.6 months). Only 46 patients (51%) completed all 5 years of therapy. Thus, 49% of patients stopped treatment early because of patient choice (21%), adverse events (16%), or other reasons (12%).

PERSIST-5 (NCT00867113) was a single-arm phase II trial of 91 patients with fully resected, high-risk GISTs. Patients received imatinib (400 mg daily) for up to 5 years.[15][Level of evidence C1]

At a median follow-up of 19.6 months, the estimated 5-year RFS rate was 90% (95% CI, 80%–95%). The OS rate was 95% (95% CI, 86%–99%). Seven patients (7.6%) had a recurrence, 6 of which occurred after treatment discontinuation.

A small, single-institution, retrospective analysis included 234 patients with R0-resected GISTs at moderate to high risk of recurrence. The study evaluated the effect of differing durations of postoperative imatinib on 5-year RFS and OS rates.[13][Level of evidence C1]

A small, single-institution, retrospective analysis included 234 patients with R0-resected GISTs at moderate to high risk of recurrence. The study evaluated the effect of differing durations of postoperative imatinib on 5-year RFS and OS rates.[13][Level of evidence C1]

At a median follow-up of 54 months, the 5-year RFS rate across all groups was 76.2%. The OS rate across all groups was 83.4%.

A small, single-institution, retrospective analysis included 234 patients with R0-resected GISTs at moderate to high risk of recurrence. The study evaluated the effect of differing durations of postoperative imatinib on 5-year RFS and OS rates.[13][Level of evidence C1]

In high-risk patients, longer durations of imatinib therapy were associated with higher RFS rates (36.5% in the 1-year group, 68.7% in the 1–3-years group, 71.2% in the 3–5-years group, and 90.8% in the >5-years group; P < .001). Longer imatinib therapy duration was also associated with higher OS rates (36.7% in the 1-year group, 76.6% in the 1–3-years group, 84.0% in the 3–5-years group, and 97.4% in the >5-years group; P < .001).