Midostaurin

In a randomized, placebo-controlled, phase III study (CALGB10603/RATIFY [NCT00651261]) of 717 adults aged 18 to 59 years with AML and FLT3 ITD or TKD variants, standard chemotherapy was given with or without midostaurin (50 mg/dose twice daily) followed by maintenance midostaurin or placebo for patients who did not proceed to HSCT.[28]

In a randomized, placebo-controlled, phase III study (CALGB10603/RATIFY [NCT00651261]) of 717 adults aged 18 to 59 years with AML and FLT3 ITD or TKD variants, standard chemotherapy was given with or without midostaurin (50 mg/dose twice daily) followed by maintenance midostaurin or placebo for patients who did not proceed to HSCT.[28]

OS (the primary end point) and EFS were significantly better for patients who received midostaurin.

In a randomized, placebo-controlled, phase III study (CALGB10603/RATIFY [NCT00651261]) of 717 adults aged 18 to 59 years with AML and FLT3 ITD or TKD variants, standard chemotherapy was given with or without midostaurin (50 mg/dose twice daily) followed by maintenance midostaurin or placebo for patients who did not proceed to HSCT.[28]

The median OS was 74.7 months (95% confidence interval [CI], 31.5–not reached) for patients in the midostaurin arm versus 25.6 months (95% CI, 18.6–42.9) for patients in the control arm (hazard ratio [HR], 0.78; 95% CI, 0.63–0.96; P = .009).

In a randomized, placebo-controlled, phase III study (CALGB10603/RATIFY [NCT00651261]) of 717 adults aged 18 to 59 years with AML and FLT3 ITD or TKD variants, standard chemotherapy was given with or without midostaurin (50 mg/dose twice daily) followed by maintenance midostaurin or placebo for patients who did not proceed to HSCT.[28]

The median EFS was 8.2 months (95% CI, 5.4–10.7) for patients in the midostaurin arm versus 3.0 months (95% CI, 1.9–5.9) for patients in the control arm (HR, 0.78; 95% CI, 0.66–0.93; P = .002).

In a randomized, placebo-controlled, phase III study (CALGB10603/RATIFY [NCT00651261]) of 717 adults aged 18 to 59 years with AML and FLT3 ITD or TKD variants, standard chemotherapy was given with or without midostaurin (50 mg/dose twice daily) followed by maintenance midostaurin or placebo for patients who did not proceed to HSCT.[28]

This benefit was seen across all FLT3 subgroups regardless of whether allogeneic HSCT was used in consolidation.

A second single-arm trial in 284 adults (aged 18–70 years) with FLT3 ITD AML added midostaurin (50 mg/dose twice daily) to intensive chemotherapy followed by allogeneic HSCT or consolidation, and all patients had a subsequent midostaurin maintenance phase.[29]

A second single-arm trial in 284 adults (aged 18–70 years) with FLT3 ITD AML added midostaurin (50 mg/dose twice daily) to intensive chemotherapy followed by allogeneic HSCT or consolidation, and all patients had a subsequent midostaurin maintenance phase.[29]

The 2-year EFS rate was 37.7% (95% CI, 32%–44.3%), and the OS rate was 50.9% (95% CI, 44.9%–57.6%).

A second single-arm trial in 284 adults (aged 18–70 years) with FLT3 ITD AML added midostaurin (50 mg/dose twice daily) to intensive chemotherapy followed by allogeneic HSCT or consolidation, and all patients had a subsequent midostaurin maintenance phase.[29]

Using a historical-control comparison, significant improvement in EFS was reported (HR, 0.58; 95% CI, 0.48–0.70; P < .001).