AML Drug Midostaurin Wins Breakthrough Therapy Designation

Kinase inhibitor improves survival in phase III trial

The FDA has granted a breakthrough therapy designation to midostaurin (PKC412, Novartis) for the treatment of adults with newly diagnosed acute myeloid leukemia (AML) who are FMS-like tyrosine kinase-3 (FLT3) mutation-positive, as detected by an FDA-approved test, and who are eligible to receive standard induction and consolidation chemotherapy.

The breakthrough therapy designation for midostaurin was primarily based on positive results from the phase III RATIFY trial. In that study, patients who received midostaurin and standard induction and consolidation chemotherapy experienced a significant improvement in overall survival (hazard ratio, 0.77; P = 0.0074) compared with those who received standard induction and consolidation chemotherapy alone. The median overall survival for patients in the midostaurin group was 74.7 months compared with 25.6 months for those in the chemotherapy group. No statistically significant differences were observed in the overall rate of grade-3 or higher hematological and nonhematological adverse events in midostaurin-treated patients compared with those given chemotherapy. A total of 37 deaths were reported, with no difference in treatment-related deaths observed between the two groups.

AML is an aggressive cancer of the blood and bone marrow that prevents white blood cells from maturing. This results in the accumulation of “blasts,” which do not allow room for normal blood cells. AML is the most common acute leukemia in adults, and it also has the lowest survival rate. AML accounts for approximately 25% of all adult leukemias worldwide, with the highest incidence rates occurring in the U.S., Europe, and Australia.

Mutations in specific genes are found in many cases of AML, and biomarker testing is considered the standard of care for newly diagnosed patients to help determine the best treatment option. FLT3 is a receptor tyrosine kinase (a type of cell-surface receptor) that plays a role in the proliferation of certain blood cells.

Midostaurin is an investigational, oral, multitargeted kinase inhibitor in development for the treatment of patients with AML with an FLT3 mutation. The treatment’s safety and efficacy have not been fully established. There is no guarantee that midostaurin will become commercially available.

Midostaurin is also being investigated for the treatment of patients with aggressive systemic mastocytosis/mast cell leukemia.

Source: Novartis; February 19, 2016.