The targeted agent, midostaurin, has demonstrated a survival improvement among patients with acute myeloid leukemia (AML) that has the TMS-like tyrosine kinase 3 (FLT3) mutation. These results were presented at a plenary session at the 2015 annual meeting of the American Society of Hematology (ASH), in Orlando, Florida.
Acute myeloid leukemia is a type of cancer that starts in blood cells. It is a type of leukemia that often requires fairly aggressive types of treatment to provide a cure.
Recently, researchers have discovered different genetic mutations within AML cancer cells that confer differing prognoses. For example, the FLT3 mutation occurs in approximately 30%-35% of patients with AML and is associated with a poorer prognosis among patients with this disease.
Midostaurin is an agent that is targeted specifically against the FLT3 mutation. It produces its anti-cancer effects through blocking mechanisms associated with the aggressiveness of the cancer caused by the FLT3 mutation.
Researchers recently conducted a phase III clinical trial to evaluate midostaurin in the treatment of patients with AML who had the FLT3 mutation. The trial included 717 patients, aged between 18 and 60 years. Patients were treated with either standard therapy (chemotherapy consisting of daunorubicin and cytarabine) plus placebo (inactive substitute), or standard therapy with the addition of midostaurin.
Median follow-up was 57 months.
- Median overall survival was 74.7 months for patients treated with the addition of midostaurin, compared with 25.6 months who were treated with standard therapy.
- At 5 years, the survival rate was 50.9% for patients treated with midostaurin, compared with 43.9% for those treated with standard therapy.
Midostaurin is the first agent in approximately 30 years that has demonstrated a survival benefit over standard chemotherapy in the treatment of AML.
Second-generation agents that are targeted specifically against the FLT3 mutation are also in clinical trials for the treatment of patients with AML in the hopes that outcomes can be improved further.
Reference: Stone R, Mandrekar S, Sanford B, et al. The Multi-Kinase Inhibitor Midostaurin (M) Prolongs Survival Compared with Placebo (P) in Combination with Daunorubicin (D)/Cytarabine (C) Induction (ind), High-Dose C Consolidation (consol), and As Maintenance (maint) Therapy in Newly Diagnosed Acute Myeloid Leukemia (AML) Patients (pts) Age 18-60 with FLT3 Mutations (muts): An International Prospective Randomized (rand) P-Controlled Double-Blind Trial (CALGB 10603/RATIFY [Alliance]. Proceedings from the 2015 annual meeting of the American Society of Hematology. Abstract #6.