Midostaurin

In the multicenter, randomized, phase III RATIFY trial (NCT00651261), the FLT3/multikinase inhibitor midostaurin plus cytarabine and daunorubicin induction chemotherapy was compared with placebo in patients with FLT3-altered AML.[16][Level of evidence A1]While maintenance was well tolerated in the RATIFY study, only a small subset of patients tolerated midostaurin as maintenance therapy after chemotherapy or transplant in a separate phase II study.[18]

In the multicenter, randomized, phase III RATIFY trial (NCT00651261), the FLT3/multikinase inhibitor midostaurin plus cytarabine and daunorubicin induction chemotherapy was compared with placebo in patients with FLT3-altered AML.[16][Level of evidence A1]While maintenance was well tolerated in the RATIFY study, only a small subset of patients tolerated midostaurin as maintenance therapy after chemotherapy or transplant in a separate phase II study.[18]

The addition of the FLT3/multikinase inhibitor midostaurin to cytarabine and daunorubicin induction chemotherapy led to improved survival (median, 75 vs. 26 months; hazard ratio [HR] for death, 0.78; one-sided P = .009).

In the multicenter, randomized, phase III RATIFY trial (NCT00651261), the FLT3/multikinase inhibitor midostaurin plus cytarabine and daunorubicin induction chemotherapy was compared with placebo in patients with FLT3-altered AML.[16][Level of evidence A1]While maintenance was well tolerated in the RATIFY study, only a small subset of patients tolerated midostaurin as maintenance therapy after chemotherapy or transplant in a separate phase II study.[18]

Patients who remained in remission after completion of consolidation therapy entered a maintenance phase in which they received midostaurin or placebo, administered at a dose of 50 mg orally twice daily, for twelve 28-day cycles. A maintenance regimen was administered for the full 12 cycles in 120 patients (69 in the midostaurin group, and 51 in the placebo group).

In the multicenter, randomized, phase III RATIFY trial (NCT00651261), the FLT3/multikinase inhibitor midostaurin plus cytarabine and daunorubicin induction chemotherapy was compared with placebo in patients with FLT3-altered AML.[16][Level of evidence A1]While maintenance was well tolerated in the RATIFY study, only a small subset of patients tolerated midostaurin as maintenance therapy after chemotherapy or transplant in a separate phase II study.[18]

An ad-hoc landmark analysis from the end of maintenance revealed no difference in DFS between the two arms. Moreover, from the start of maintenance therapy there was no difference in OS between the two arms.[17]

In the multicenter, randomized phase II RADIUS trial (NCT01883362), the addition of midostaurin to standard of care was compared with standard of care alone after allogeneic HCT.[19] Similar to the RATIFY trial, midostaurin was administered at a dose of 50 mg orally twice daily, for twelve 28-day cycles. Thirty patients were enrolled in each arm, but only half were able to complete the entire 12 cycles of therapy.

In the multicenter, randomized phase II RADIUS trial (NCT01883362), the addition of midostaurin to standard of care was compared with standard of care alone after allogeneic HCT.[19] Similar to the RATIFY trial, midostaurin was administered at a dose of 50 mg orally twice daily, for twelve 28-day cycles. Thirty patients were enrolled in each arm, but only half were able to complete the entire 12 cycles of therapy.

The estimated 18-month relapse-free survival (RFS) rate was 89% in the midostaurin arm and 76% in the standard of care arm (HR, 0.46; 95% confidence interval [CI], 0.12−1.86; P = 0.27). The predicted relative reduction in the risk of relapse with the addition of midostaurin was 54%.[19][Level of evidence B1]