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According to researchers, these “results suggest that both schedules of decitabine are safe and effective in the population assessed.”
A randomized phase 2 trial of decitabine schedules in older patients with newly diagnosed acute myeloid leukemia (AML) found that efficacy and safety did not differ between a 5-day or 10-day decitabine schedule.
The study, published in The Lancet Haematology, also did not identify a subgroup that benefited preferentially from either schedule of decitabine, including patients with TP53mut AML.
“Our results suggest that both schedules of decitabine are safe and effective in the population assessed and could be considered as reasonable non-intensive backbone regimens for future investigational combinations with novel agents,” the authors wrote.
Patients included in the trial were aged 60 years or older with AML, but unsuitable for intensive chemotherapy (or <60 years if unsuitable for intensive chemotherapy with an anthracycline plus cytarabine). The composite primary end points were complete remission (CR), complete remission with incomplete platelet recovery (CRp), and complete remission with incomplete hematological recovery (CRi) achieved at any time and assessed by intention to treat.
Trial participants received 20 mg/m2 of decitabine intravenously for either 5 or 10 consecutive days as induction therapy every 4 to 8 weeks for up to 3 cycles. Patients who responded received decitabine as consolidation therapy on a 5-day schedule for up to 24 cycles. Notably, the first 40 patients were randomized equally to the 2 treatment groups, after which a response-adaptive randomization algorithm used all previous patients’ treatment and response data to determine the placement of each following patient favoring the group with superior response.
Between Feb 28, 2013 and April 12, 2018, 71 patients were enrolled in the study, including 28 who received decitabine for 5 days and 43 for 10 days. Total follow-up was 38.2 months, during which the median duration of overall survival (OS) was 5.5 months (IQR 2.1-11.7) in the 5-day group and 6.0 months (1.9-11.7) in the 10-day group. Moreover, 1-year OS was 25% in both groups. Overall, the primary end point was achieved in comparable proportions of patients in the 2 treatment cohorts (12 [43%] of 28 in the 5-day schedule group, 95% CI, 26-60, and 17 [40%] of 43 in the 10-day schedule group, 26-54, P = 0.78; difference 3%, -21 to 27).
When stratified by cytogenetics, de-novo versus secondary or therapy-related AML, or TP53mut status, CR, CRp, CRi, and OS did not differ between groups.
“Our study has relevance to the optimum duration of decitabine therapy in future combination regimens and suggests that 5-day and 10-day regimens are equivalent in efficacy,” the authors explained. “These results also have implications for the delivery of cost-effective care, as they suggest that additional doses of decitabine could raise treatment costs without providing additional benefit.”
The most common grade 3-4 adverse events (AEs) observed were neutropenic fever (7 patients [25%] in the 5-day group and 14 [33%] in the 10-day group) and infection (5 [18%] and 16 [37%], respectively). Further, 1 patient (4%) died from sepsis in correlation with neutropenic fever, infection, and hemorrhage in the 5-day group, and in the 10-day group 6 patients (14%) died from infection. Early mortality was similar between the 2 groups.
Importantly, azacytidine is also commonly used as a first-line treatment for this patient population, and no large randomized trials have been done to compare decitabine and azacitidine in this setting; therefore, it is currently unclear as to which hypomethylating agent is superior. In addition, the researchers suggested these results may not directly translate to patients with relapsed or refractory AML.
“Future prospective studies in patients with relapsed or refractory disease will be needed to clarify the outcomes,” the authors noted.
Short NJ, Kantarjian HM, Loghavi S, et al. Treatment with a 5-day versus a 10-day schedule of decitabine in older patients with newly diagnosed acute myeloid leukaemia: a randomised phase 2 trial. The Lancet Haematology. doi: 10.1016/S2352-3026(18)30182-0