Phase III RATIFY trial of PKC 412 (midostaurin) success for FLT3-mutated acute myeloid leukemia (AML)- Novartis
Novartis has announced positive results from the global Phase III RATIFY (CALGB 10603) clinical trial. In the study, adult patients under 60 years of age with newly-diagnosed FLT3-mutated acute myeloid leukemia (AML) who received the investigational compound PKC 412 (midostaurin) plus standard induction and consolidation chemotherapy experienced a 23% improvement in overall survival (OS) (hazard ratio [HR] = 0.77, P = 0.0074) compared to those treated with standard induction and consolidation chemotherapy alone. The median OS for patients in the PKC 412 (midostaurin) treatment group was 74.7 months (95% confidence interval [CI]: 31.7, not attained), versus 25.6 months (95% CI: 18.6, 42.9) for patients in the placebo group.
The trial evaluated the addition of either PK C412 (midostaurin) or placebo to daunorubicin/cytarabine in the induction phase, followed by high-dose cytarabine in the consolidation phase; patients who achieved complete remission after consolidation chemotherapy continued treatment with PKC 412 (midostaurin) or placebo as a single agent for up to one year.
In addition to meeting the primary endpoint of OS, event free survival (EFS, defined as the earliest death, relapse or no complete response within 60 days of the start of induction therapy) was significantly higher in the PKC412 (midostaurin) treatment group versus the placebo group [HR = 0.79, P = 0.0025 and median of 8.0 months (95% CI: 5.14, 10.6) vs. 3.0 months (95% CI: 1.9, 5.9)] .
The data, collected and analyzed in partnership with the Alliance for Clinical Trials in Oncology, are from the largest clinical trial in FLT3-mutated AML to date, with 3,279 patients screened and 717 study participants from around the world. Results will be presented at the 57th American Society of Hematology (ASH) Annual Meeting in Orlando, Florida, .
Comment:Approximately 30% of patients with AML have a genetic mutation within the FLT3 gene. A mutation within the FLT3 gene results in continuous signals to the cancer cells, causing them to grow in an uncontrolled manner, and preventing them from natural death. These patients have a poorer survival than other patients with AML treated with standard therapeutic approaches. PKC 412 is an agent that blocks the growth signal caused by the FLT3 mutation, resulting in cellular death.
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