Results from a randomized phase III trial of decitabine versus supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed AML.

6504 Background: We conducted a Phase 3 trial, the largest to date in older patients with acute myeloid leukemia (AML), comparing decitabine (DAC) to patient's choice with physician's advice (treatment choice – TC) of supportive care (SC) or low-dose cytarabine (AraC). Methods: In this open-label Phase 3 trial, newly diagnosed patients ≥65 years of age with de novo or secondary AML and poor- or intermediate-risk cytogenetics were randomized to two treatment groups: TC: either SC or 20 mg/m2 AraC subcutaneously once daily for 10 consecutive days, every 4 weeks; or DAC 20 mg/m2 as a 1-hour IV infusion once daily for 5 consecutive days, every 4 weeks. The primary endpoint was overall survival (OS). Results: Of 485 enrolled patients, 242 were randomized to DAC and 243 to TC. DAC patients had a median duration of treatment of 4.4 months versus 2.4 months for those on the TC arm. The protocol-specified final analysis with 396 (81.6%) deaths showed a statistically non-significant but favorable trend for increased OS for patients treated with DAC, with a median survival of 7.7 months (95% CI: 6.2, 9.2) versus 5.0 months (95% CI: 4.3, 6.3) in the TC arm. The HR was 0.85 (95% CI: 0.69, 1.04), and p=0.10. An updated unplanned OS analysis with 446 (92%) deaths showed the same median survival with strengthened evidence of the DAC effect (HR 0.82; 95% CI: 0.68, 0.99; nominal p=0.03). The secondary endpoint of CR+CRp rate was 18% (DAC) versus 8% (TC) with OR=2.5 (95% CI: 1.4, 4.8) and p=0.001. AE rates were consistent with the known DAC safety profile and without major differences between the treatment arms. The most frequently reported Grade 3 or 4 hematologic AEs were thrombocytopenia, anemia, neutropenia, and febrile neutropenia. Conclusions: Compared with the accepted standard therapies used in this study to treat older patients with AML, DAC showed an overall survival advantage and higher response rates without major differences in safety.