Table 4.
Summary of Studies Evaluating the Efficacy of Imatinib for the Treatment of Recurrent or Metastatic Gastrointestinal Stromal Tumors
| Study and Design | Treatment | Patients | Efficacy |
|---|---|---|---|
| B2222 trial (Blanke 200835); phase 2, MC, R, OL | Im 400 or 600 mg/da | Advanced unresectable or metastatic GIST; KIT +ve; ECOG PS ≤3; ≥1 measurable tumor not previously treated with chemotherapy or embolization; N = 147 (evaluable) | Median FU 9.6 mo (combined data for both doses)b; all patients: CR (0%), PR (53.7%), SD (27.9%), PD (13.6%); estimated 1-y OS, 88%; median FU 63 mo (combined data for both doses)b CR (1.4%), PR (66.7%), SD (15.6%), PD (11.6%); median OS, 57 mo |
| S0033 trial (Blanke 200836); phase 3, MC, R, OL | Im 400 mg qd or bida | Metastatic or surgically unresectable disease; KIT +ve; Zubrod PS, 0–3; N = 694 | Median FU 4.5 yb median PFS (primary endpoint), 18 mo (400 mg), 20 mo (800 mg); median OS (primary endpoint): 55 mo (400 mg), 51 mo (800 mg); 400 mg: CR (5%), PR (40%), SD (25%), PD (12%); 800 mg: CR (3%), PR (42%), SD (22%), PD (10%) |
| EORTC 62005 trial (Verweij 2004,37 Casali 200538); phase 3, MC, R | Im 400 mg qd or bida | Advanced or metastatic disease; KIT +ve; WHO PS <4; N = 946 | Median FU 25.3 mo: PFS (primary endpoint): 44% (400 mg) vs 50% (800 mg; HR, 0.82; 95% CI, 0.69–0.98; P = .026); median FU 40 mo (combined data for both doses)b median PFS, 22 mo; 3-y OS, 59%; 3-y PFS, 33% |
| MetaGIST (Van Glabbeke 200739); meta-analysis of S0033 and EORTC 62005 trials | Im 400 mg qd or bida | The same as S0033 and EORTC 62005; N = 1640 | Median FU 45 mo: Im 800 mg small but significant advantage vs Im 400 mg for PFS; OS comparable for both doses; KIT exon 9 mutations, Im 800 mg benefit for PFS and OS vs Im 400 mg |
MC indicates multicenter; R, randomized; OL, open label; Im, imatinib; GIST, gastrointestinal stromal tumor; KIT, v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog; +ve, positive; ECOG, Eastern Cooperative Oncology Group; PS, performance status; FU, follow-up; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; OS, overall survival; qd, once daily; bid, twice daily; PFS, progression-free survival; EORTC, European Organization for Research and Treatment of Cancer; WHO, World Health Organization; HR, hazard ratio; MetaGIST, GIST Meta-Analysis Group. KIT v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog
Patients were crossed over to the higher Im dose if they progressed on the lower dose.
There was no significant difference between the 2 dose groups for any endpoint.