Prospective randomized trials of chemotherapy plus an FLT3 inhibitor in patients with mutant FLT3 ITD AML
| Trial . | Comparison vs placebo . | No. . | Age, y . | Primary end point . | Notes . |
|---|---|---|---|---|---|
| C10603/RATIFY | Midostaurin | 717, 555 ITD | 18-59 | OS: 74.7 vs 25.6 mo; HR, 0.78 (95% CI, 0.63-0.96), 1P = .009 | OS in ITD only (HR, 0.81 [95% CI, 0.58-1.12], P = .19). OS in CR1 alloSCT: 28.1 vs 22.7 mo, P = .07 Only grade 3-5 tox in mido: rash (14% vs 5%) |
| UK MRC 15/17 | Lestaurtinib | 500, 385 ITD | 18-60 | OS: 5 y, 46% vs 44.8%, HR, 0.9 (95% CI, 0.7-1.18), P = .4 | FLT3 not frequently suppressed. Benefit observed in those who received GO + azole |
| QUANTUM-FIRST | Quizartinib | 539 ITD | 18-75 | OS: 31.9 vs 15.1 mo, HR, 0.78, 2P = .032 | Grade 5 infections: 8% quizartinib vs 4% P; in age <60 y, med OS: HR, 0.68 (95% CI, 0.49-0.95) |
| ALLG | Sorafenib | 98 ITD | 18-65 | 2-y EFS: 47.9% vs 45.9%, HR, 0.87 (95% CI, 0.51-1.51), P = .61 | 2-y OS in patients who received CR1 tx: 84% vs 67%, HR, 0.45 (95% CI, 0.18-1.12), P = .08 NPM1 mut 81% in P, 60% in sorafenib |
| Trial . | Comparison vs placebo . | No. . | Age, y . | Primary end point . | Notes . |
|---|---|---|---|---|---|
| C10603/RATIFY | Midostaurin | 717, 555 ITD | 18-59 | OS: 74.7 vs 25.6 mo; HR, 0.78 (95% CI, 0.63-0.96), 1P = .009 | OS in ITD only (HR, 0.81 [95% CI, 0.58-1.12], P = .19). OS in CR1 alloSCT: 28.1 vs 22.7 mo, P = .07 Only grade 3-5 tox in mido: rash (14% vs 5%) |
| UK MRC 15/17 | Lestaurtinib | 500, 385 ITD | 18-60 | OS: 5 y, 46% vs 44.8%, HR, 0.9 (95% CI, 0.7-1.18), P = .4 | FLT3 not frequently suppressed. Benefit observed in those who received GO + azole |
| QUANTUM-FIRST | Quizartinib | 539 ITD | 18-75 | OS: 31.9 vs 15.1 mo, HR, 0.78, 2P = .032 | Grade 5 infections: 8% quizartinib vs 4% P; in age <60 y, med OS: HR, 0.68 (95% CI, 0.49-0.95) |
| ALLG | Sorafenib | 98 ITD | 18-65 | 2-y EFS: 47.9% vs 45.9%, HR, 0.87 (95% CI, 0.51-1.51), P = .61 | 2-y OS in patients who received CR1 tx: 84% vs 67%, HR, 0.45 (95% CI, 0.18-1.12), P = .08 NPM1 mut 81% in P, 60% in sorafenib |
alloSCT, allogeneic stem cell transplant; CI, confidence interval; CR1, first complete remission; EFS, event-free survival; GO, gemtuzumab ozagamicin; HR, hazard ratio; med, median; mido, midostaurin; mut, mutation; OS, overall survival; P, placebo; 1P, 1-sided P test; 2P, 2-sided P test; tox, toxicity; tx, transplant.