Guadecitabine benefits older patients with untreated AML
medwireNews: Older patients with untreated acute myeloid leukemia (AML) respond well to the next-generation hypomethylating drug guadecitabine, with more than half achieving a composite complete response in a phase II trial of different drug doses and schedules.
Based on their findings, the researchers recommend a guadecitabine regimen of 60 mg/m2 in a 5-day schedule for patients aged 65 years and older with treatment-naïve AML who are not candidates for intensive chemotherapy.
The multicenter study included 107 patients who met these criteria. They were randomly assigned to receive treatment with guadecitabine 60 mg/m2 (n=26) or 90 mg/m2 (n=28) on days 1–5 of a 28-day cycle (5-day schedule). A further 53 patients were later assigned to receive 60 mg/m2 on days 1–5 and 8–12 of a 28-day cycle (10-day schedule) on the basis of emerging favourable data from a 10-day schedule in patients with relapsed or refractory AML.
As reported in The Lancet Oncology, there was no significant difference between the treatment schedules in the proportion of patients who achieved a composite complete response, defined as a complete response, complete response with incomplete platelet recovery, or complete response with incomplete neutrophil recovery regardless of platelets.
Specifically, during a median follow-up period of 31.8 months, the composite complete response rate was 54% in patients treated with guadecitabine 60 mg/m2 on the 5-day schedule, 59% in those who received 90 mg/m2 on the 5-day schedule, and 50% in the group that received 60 mg/m2 on the 10-day schedule.
Hagop Kantarjian (University of Texas MD Anderson Cancer Center, Houston, USA) and co-investigators point out that 35 patients achieved a complete response after a median of four cycles in the 5-day cohort and three cycles in the 10-day cohort.
“These results highlight the importance of continuing treatment with hypomethylating agents beyond the one or two cycles usually administered with intensive induction chemotherapy, as hypomethylating agents might result in a complete response after as many as ten cycles, as shown in this report,” they write.
Median overall survival was similar among the groups, at 10.5 months for all patients on the 5-day schedule and 9.5 months for those on the 10-day schedule.
During the study, 23 patients died due to adverse events, mainly sepsis (n=8) or pneumonia (n=5); four of these deaths were deemed treatment-related (two from pneumonia, one multi-organ failure, and one sepsis, all in the 10-day cohort).
The most common serious adverse events overall were febrile neutropenia (53 vs 48% for the 5- and 10-day schedules), pneumonia (27 vs 31%), and sepsis (16 vs 27%).
“In the absence of any signal for superior activity of the higher dose or the longer daily administration (10-day schedule) compared with the biologically effective dose on the 5-day schedule, the recommended guadecitabine regimen is 60 mg/m2 per day in a 5-day schedule in this patient population,” Kantarjian et al conclude.
They add: “A phase 3 study in this patient population is ongoing to assess guadecitabine 60 mg/m2 in a 5-day schedule versus standard of care.”
In an accompanying comment, Felicetto Ferrara, from Cardarelli Hospital in Naples, Italy, says the findings show that “guadecitabine represents a potential new therapeutic option for a challenging disease in older individuals and, in the near future, could also be investigated in combination with other new drugs.”
By Laura Cowen
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