Acute Myeloid Leukemia - Trial of Xospata shows improved survival

Astellas Pharma announced results from the Phase III ADMIRAL clinical trial comparing Xospata (gilteritinib) to salvage chemotherapy in adult patients with relapsed or refractory (resistant to treatment) Acute Myeloid Leukemia (AML) with a FLT3 mutation. The results show that patients treated with Xospata had significantly longer Overall Survival (OS) than those who received standard salvage chemotherapy. Results from the ADMIRAL trial show the median OS for patients who received XOSPATA was 9.3 months compared to 5.6 months for patients who received salvage chemotherapy (Hazard Ratio = 0.637 (95% CI 0.490, 0.830), P=0.007); one-year survival rates were 37% for patients who received Xospata compared to 17% for patients who received salvage chemotherapy.

The most common treatment-emergent adverse events (TEAEs) of any grade occurring in at least 10% of patients during the first 30 days of treatment with gilteritinib were anemia (33%), increased alanine aminotransferase (24%), increased aspartate aminotransferase (24%), febrile neutropenia (21%), thrombocytopenia (19%), constipation (17%), pyrexia (15%), fatigue (15%), decreased neutrophil count (14%), increased blood alkaline phosphatase (13%), nausea (13%), hypokalemia (11%), cough (11%), headache (10%), and diarrhea (10%). The most common TEAEs of any grade occurring in greater than 10% of patients during the first 30 days of treatment with salvage chemotherapy were anemia (33%), febrile neutropenia (32%), nausea (30%), diarrhea (28%), hypokalemia (27%), pyrexia (26%), decreased appetite (17%), decreased white blood cell count (17%), thrombocytopenia (16%), constipation (14%), abdominal pain (14%), hyperglycemia (13%), headache (13%), stomatitis (13%), fatigue (11%), decreased neutrophil count (11%), increased aspartate aminotransferase (10%), vomiting (10%), peripheral edema (10%), and hypomagnesemia (10%. The data were shared at the American Association for Cancer Research (AACR) Annual Meeting.

Comment: Xospata was approved by the Japan Ministry of Health, Labor and Welfare (MHLW) for relapsed or refractory AML with FLT3 mutations and launched as Xospata 40 mg Tablets in 2018. In February 2019, a marketing authorization application (MAA) for the oral once-daily therapy Xospata for the treatment of adult patients who have relapsed or refractory AML with a FLT3 mutation was accepted by the European Medicines Agency for regulatory review.