CHICAGO—Decitabine extends overall survival and improves response rates compared with standard therapies in the treatment of older patients with newly diagnosed acute myelogenous leukemia (AML), said Xavier G. Thomas, MD, PhD.
The treatment options for older patients with AML are limited. Intensive chemotherapy is generally poorly tolerated in this group, the initial mortality rate is high (exceeding 30% at 8 weeks), the response rate to chemotherapy is poor, and relapse rates are high. Recently, DNA hypermethylation has been demonstrated in the promoter region in AML. Hypomethylating agents may affect tumor suppression genes and have been shown to be beneficial in AML cell lines, said Thomas, who is with the department of hematology, Edouard-Herriot Hospital, Lyon, France.
Among the hypomethylating agents, decitabine has been approved for patients with myelodysplastic syndrome, and has demonstrated activity in a previous phase 2 trial of patients older than 60 years with AML.
Based on these results, a phase 3 multicenter, controlled, open-label trial was designed to compare decitabine with patients’ choice of treatment on overall survival in patients 65 years and older with newly diagnosed de novo or secondary AML and poor- or intermediaterisk cytogenetics. The 485 patients enrolled were randomized to decitabine, 20 mg/m2 as a 1-hour intravenous infusion once daily for 5 consecutive days, every 4 weeks, or treatment of choice. Patients assigned to treatment of choice could select low-dose cytarabine, 20- mg/m2 subcutaneous injection once daily for 10 days, every 4 weeks (n = 243), or supportive care (n = 28).
Patients assigned to decitabine had a median duration of treatment of 4.4 months compared with 2.4 months for those on the treatment-of-choice arm.
The protocol-specified final analysis (after 396 deaths) showed a nonsignificant but favorable trend for increased overall survival for patients treated with decitabine, with a median survival of 7.7 months compared with 5.0 months in the treatment-of-choice arm (P = .10). Seventy-five patients received disease- modifying therapy after treatment failure following randomization. When these 75 patients were censored from the analysis, median overall survival improved to 8.5 months in the decitabine group and 5.3 months in the treatment-of-choice arm, corresponding to a 20% reduction in the risk of mortality in the decitabine arm, and the difference became statistically significant (P = .044).
An updated unplanned overall analysis was performed with 446 deaths, or approximately an additional year of patient follow-up. This updated analysis showed the same median survival in the 2 groups (7.7 vs 5.0 months) but the effect became significant (nominal P = .037). “This analysis increases the strength and validity of the first clinical cutoff,” said Thomas.
The secondary end point of complete remission with incomplete platelet recovery or complete remission with incomplete blood count recovery was achieved by 17.8% of the decitabine arm compared with 7.8% on treatment of choice.
Adverse event rates were consistent with the known decitabine safety profile and without major differences between the treatment arms.