Phase 3 studies of GO in newly diagnosed non-APL AML
| Study . | Disease . | N . | Age, y (median) . | Treatment . | Results . |
|---|---|---|---|---|---|
| MRC AML15112 | AML | 1113 | 0-71 (49) | ± GO (3 mg/m2) on day 1 of the first of 2 induction courses with either ADE, DA, or FLAG-IDA | No difference in ORR, TRM, relapse, or survival. Improved 5-y OS for favorable-risk subgroup (79% vs 51%; P = .0003) with GO; predicted 10% OS benefit for ∼ 70% of patients with intermediate-risk disease |
| ALFA 0701113 | AML | 278 | 59-66 (62) | ± GO (3 mg/m2) on days 1, 4, and 7 of DA induction and day 1 of each of 2 courses of DA consolidation | No difference in ORR or mortality. Improved 2-y EFS (40.8% vs 17.1%, P = .0003), DFS (50.3% vs 22.7%, P = .0003) and OS (53.2% vs 41.9%, P = .037) with GO. Survival benefit seen in favorable/intermediate- but not adverse-risk disease |
| GOELAMS AML 2006 IR114 | AML (intermediate risk) | 238 | 18-60 (50) | ± GO (6 mg/m2) on day 1 with DA induction and MA consolidation | No difference in ORR, TRM, or 3-y EFS. Improved EFS with GO in patients who did not undergo allogeneic HCT (53.7% vs 27%, P = .0308) |
| NCRI AML16115 | AML, high-risk MDS | 1115 | 51-84 (67) | ± GO (3 mg/m2) on day 1 of the first of 2 induction courses with either DA or DCLo | No difference in TRM; trend towards reduced risk of persistent disease with GO (17% vs 21%, P = .06). Reduced 3-y relapse risk (68% vs 76%; P = .007) and superior DFS (21% vs 16%; P = .04) and OS (25% vs 20%; P = .05) with GO |
| SWOG S0106116,117 | AML | 596 | 18-60 (47) | ± GO (6 mg/m2) on day 4 of the first of up to 2 induction courses with DA* | Increased TRM in GO arm (5.7% vs 1.4%; P = .01). No difference in ORR, DFS, or OS. Possible trend towards improved OS in favorable-risk subgroup with GO (hazard ratio: 0.49 [0.12–2.04]) |
| Study . | Disease . | N . | Age, y (median) . | Treatment . | Results . |
|---|---|---|---|---|---|
| MRC AML15112 | AML | 1113 | 0-71 (49) | ± GO (3 mg/m2) on day 1 of the first of 2 induction courses with either ADE, DA, or FLAG-IDA | No difference in ORR, TRM, relapse, or survival. Improved 5-y OS for favorable-risk subgroup (79% vs 51%; P = .0003) with GO; predicted 10% OS benefit for ∼ 70% of patients with intermediate-risk disease |
| ALFA 0701113 | AML | 278 | 59-66 (62) | ± GO (3 mg/m2) on days 1, 4, and 7 of DA induction and day 1 of each of 2 courses of DA consolidation | No difference in ORR or mortality. Improved 2-y EFS (40.8% vs 17.1%, P = .0003), DFS (50.3% vs 22.7%, P = .0003) and OS (53.2% vs 41.9%, P = .037) with GO. Survival benefit seen in favorable/intermediate- but not adverse-risk disease |
| GOELAMS AML 2006 IR114 | AML (intermediate risk) | 238 | 18-60 (50) | ± GO (6 mg/m2) on day 1 with DA induction and MA consolidation | No difference in ORR, TRM, or 3-y EFS. Improved EFS with GO in patients who did not undergo allogeneic HCT (53.7% vs 27%, P = .0308) |
| NCRI AML16115 | AML, high-risk MDS | 1115 | 51-84 (67) | ± GO (3 mg/m2) on day 1 of the first of 2 induction courses with either DA or DCLo | No difference in TRM; trend towards reduced risk of persistent disease with GO (17% vs 21%, P = .06). Reduced 3-y relapse risk (68% vs 76%; P = .007) and superior DFS (21% vs 16%; P = .04) and OS (25% vs 20%; P = .05) with GO |
| SWOG S0106116,117 | AML | 596 | 18-60 (47) | ± GO (6 mg/m2) on day 4 of the first of up to 2 induction courses with DA* | Increased TRM in GO arm (5.7% vs 1.4%; P = .01). No difference in ORR, DFS, or OS. Possible trend towards improved OS in favorable-risk subgroup with GO (hazard ratio: 0.49 [0.12–2.04]) |
ADE indicates cytarabine/daunorubicin/etoposide; DA, daunorubicin/cytarabine; DClo, daunorubicin/clofarabine; DFS, disease-free survival; EFS, event-free survival; FLAG-Ida, fludarabine/cytarabine/G-CSF/idarubicin; HCT, hematopoietic cell transplantation; MA, mitoxantrone/cytarabine; ORR, overall response rate (CR + CRi); OS, overall survival; and TRM, treatment-related mortality.
Daunorubicin was used at 60 mg/m2/d in the control arm and 45 mg/m2/d in the GO arm.