Table 2.
The most important clinical trials of adjuvant therapy with imatinib in gastrointestinal stromal tumors (GISTs)
| Study | Study design | No. of patients | Major eligibility criteria | Results | |
|---|---|---|---|---|---|
| Primary endpoint | Secondary endpoints | ||||
| ACOSOG Z9000, DeMatteo et al. 2009 [98] | One arm, open, multicenter; imatinib 400 mg daily for 1 year | 107 | Primary GIST KIT-positive after radical resection; high risk of relapse: tumor size ≥10 cm OR tumor rupture OR <5 intraperitoneal metastases | OS at median follow-up of 4 years; 1-year OS: 99 %; 2-year OS: 97 %; 3-year OS: 97 % | RFS at median follow-up of 4 years; 1-year RFS: 94 %; 2-year RFS: 73 %; 3-year RFS: 61 % |
| Kang et al. 2009 [97] | One arm, open, multicenter, prospective; imatinib 400 mg daily for 2 years | 47 | Primary GIST with exon 11 KIT mutation after radical resection; high risk of relapse: tumor size ≥10 cm OR mitotic index ≥10/50 HPFs OR tumor size ≥5 cm and mitotic index ≥5/50 HPFs | RFS at median follow-up of 26.9 months; 1-year RFS: 97.7 %; 2-year RFS: 92.7 % | |
| Li et al. 2011 [93]a | Open, non-randomized, prospective, one center; imatinib 400 mg daily for 3 years versus observation | 56 (imatinib), 49 (observation) | Primary GIST KIT-positive after resection; intermediate or high risk of recurrence (NIH classification): tumor size >5 cm AND/OR mitotic index >5/50 HPFs | Significantly better RFS in the imatinib arm as compared with observation at median follow-up of 45 months (HR 0.188, 95 % CI 0.085–0.417; p < 0.001); 1-year RFS: 100 versus 90 %; 2-year RFS: 96 versus 57 %; 3-year RFS: 89 versus 48 % | Significantly decreased risk of death due to GIST with adjuvant imatinib therapy in comparison with observation at median follow-up of 45 months (HR 0.254, 95 % CI 0.070–0.931; p = 0.025) |
| Jiang et al. 2011 [92]a | Non-randomized, one center, prospective; imatinib 400 mg daily for 5 years versus observation | 35 (imatinib), 55 (observation) | Primary GIST KIT-positive after R0 resection; high risk of relapse (modified NIH classification) | Significantly better RFS with imatinib as compared with observation at median follow-up of 44.0 months (HR 0.122, 95 % CI 0.041–0.363; p < 0.001); 1-year RFS: 100 versus 70.9 %; 2-year RFS: 88.0 versus 37.8 %; 3-year RFS: 88.0 versus 27.5 % | |
| ACOSOG Z9001, DeMatteo et al. 2009 [76, 86] | Double-blind, placebo-controlled, randomized, multicenter; imatinib 400 mg daily versus placebo for 1 year | 359 (imatinib), 354 (placebo) | Primary GIST KIT-positive after radical resection; tumor size ≥3 cm; low, intermediate, or high risk of relapse | Significant improvement in 1-year RFS in the imatinib arm (98 %) as compared with placebo (83 %); median follow-up time 19.7 months; HR 0.35; p < 0.0001 | Lack of statistically significant difference in 1-year OS between study arms (HR 0.66; p = 0.47) |
| SSGXVIII/AIO, Joensuu et al. 2012 [7, 65]a | Two arms, open, randomized, multicenter, prospective; imatinib 400 mg daily for 1 versus 3 years | 200 (1 year), 200 (3 years) | Primary GIST KIT-positive after radical resection; high risk of relapse (modified NIH classification): tumor size >10 cm OR mitotic index >10/50 HPFs OR mitotic index >5/50 and tumor size >5 cm OR tumor rupture | Significant improvement in RFS with 3-year imatinib therapy as compared with 1-year therapy at median follow-up of 54 months (HR 0.46, 95 % CI 0.32–0.65; p < 0.0001); 5-year RFS: 65.6 versus 47.9 % | Significant improvement in OS with 3-year imatinib therapy as compared with 1-year therapy at median follow-up of 54 months (HR 0.45, 95 % CI 0.22–0.89; p = 0.019); 5-year OS: 92.0 versus 81.7 % |
| EORTC 62024, Hohenberger at al. 2012 [99] | Two arms, open, randomized, multicenter, prospective; imatinib 400 mg daily for 2 years versus observation | 906 | Primary GIST KIT-positive after radical resection; intermediate or high risk of relapse (NIH classification): tumor size >5 cm AND/OR mitotic index >5/50 HPFs | Time to imatinib failure at relapse (changed from OS) | RFS, OS, safety: results are expected in 2013 |
ACOSOG American College of Surgeons Oncology Group, AIO Arbeitsgemeinschaft Internistische Onkologie, CI confidence interval, EORTC European Organization for Research and Treatment of Cancer, HPFs high-powered fields, HR hazard ratio, KIT v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog, NIH National Institutes of Health, OS overall survival, R0 microscopically radical resection of the tumor, RFS recurrence-free survival, SSG Scandinavian Sarcoma Group
aStudies evaluating adjuvant therapy with imatinib for at least 3 years