The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) recommended that the European Commission approve the FLT3 inhibitor midostaurin for the treatment of patients with FLT3-mutated acute myeloid leukemia (AML) or advanced systemic mastocytosis.
The recommendation for AML was based on data from the phase III RATIFY trial, in which patients with newly diagnosed AML who were treated with midostaurin had a 23 percent lower risk of death than patients who received a placebo. Midostaurin treatment also extended patients' median overall survival (74.7 months vs. 25.6 months; hazard ratio = 0.77 [95% CI 0.63-0.95]; p=0.0078). The most common adverse events (AEs) associated with midostaurin were febrile neutropenia, nausea, exfoliative dermatitis, vomiting, headache, petechiae, and pyrexia.
The recommendation for advanced systemic mastocytosis was based on two single-arm, open-label studies in which midostaurin-treated patients had an overall response rate of 59.6 percent (95% CI 48.6-69.8). The most common AEs associated with midostaurin were nausea, vomiting, diarrhea, peripheral edema, and fatigue.
If approved, midostaurin would be indicated in AML for use in combination with standard daunorubicin and cytarabine induction and high-dose cytarabine consolidation chemotherapy. Although the RATIFY trial enrolled patients up to age 60, the FDA label is not age-restricted and the EMA label would likely be similar.
Sources: Novartis press release, July 21, 2017; Reuters, July 21, 2017.