Previously, the tyrosine kinase inhibitor sorafenib in combination with the demethylating agent 5-azacytidine was found to be safe and effective in patients with relapsed/refractory FLT3-ITD– positive acute myeloid leukemia (AML). Researchers sought to determine whether this combination is also safe and effective in older, untreated FLT3-ITD–positive patients with AML.
Inclusion criteria included FLT3-ITD–positive patients aged 60 years and older with Eastern Cooperative Oncology Group performance status ≤2. Patients were treated with azacytidine 75 mg/m2 daily for 7 days and sorafenib 400 mg twice daily for 28 days. A total of 28 patients with untreated AML were enrolled, the majority (64%) of whom had normal karyotype.
All 28 patients were evaluable; the overall response rate (ORR) was 79% (n = 22), of which 20 (71%) achieved complete remission (CR) or CR with incomplete platelet or blood count recovery, and 2 (7%) with partial response. The median number of cycles to achieve response was 2. After a median follow-up of 4.2 months, 5 patients are alive. The median overall survival (OS) for the entire group is 8.1 months compared with 9.1 months in the 22 responders.
Evaluable patients treated with azacytidine plus sorafenib were compared with a matched cohort of historical FLT3-ITD–positive patients aged 60 years and older who were treated with hypomethylator-based therapy without sorafenib (n = 14). In the 2 patient populations, ORR and median OS were found to be similar. However, the remission duration for the responding patients treated with azacytidine plus sorafenib was significantly longer (14.5 months) than those of other hypomethylating agent regimens without sorafenib (3.8 months; P = 0.01). Safety profiles were similar for the 2 cohorts.
The researchers concluded that the combination of azacytidine and sorafenib is both well-tolerated and effective in older, untreated patients with FLT3-ITD–positive AML.
Ohanian M, et al. ASCO Abstract 7029.