Opinion
Video
All-Oral AML Therapy: Decitabine-Cedazuridine Plus Venetoclax
Author(s):
A panelist discusses how the ASCERTAIN-V study demonstrated that an all-oral combination of decitabine-cedazuridine plus venetoclax achieved a 47% complete response rate and 15.5-month median overall survival in older, unfit AML patients, representing a potential new standard of care that eliminates the need for intravenous infusions and significantly reduces clinic time burden while serving as a backbone for future oral combination therapies.
The ASCERTAIN-V study presented at ASCO 2025 evaluated an all-oral combination therapy for older, unfit patients with acute myeloid leukemia (AML). The study utilized oral decitabine-cedazuridine, which is pharmacokinetically equivalent to intravenous decitabine, combined with venetoclax as frontline treatment. This multiphase study included phase 1, 2A, and 2B components, with the ASCO presentation focusing on phase 2B results. The trial enrolled 101 patients who received standard venetoclax ramp-up dosing (100 mg, 200 mg, and 400 mg by day 3) with a 5-day regimen of oral decitabine, designed to eliminate the need for patients to visit clinics 7 days monthly for intravenous azacitidine infusions.
The study demonstrated promising efficacy and safety outcomes. The complete remission rate reached 47%, significantly exceeding the primary end point and surpassing the expected 18% rate with decitabine monotherapy. Median overall survival was 15.5 months, comparable to the VIALE-A trial results, with durable responses as 75% of patients achieving complete remission remained in remission at 12 months. Safety profiles were manageable, with febrile neutropenia and myelosuppression being the most common adverse events, consistent with azacitidine-venetoclax treatment expectations. The study revealed an important trend of reducing venetoclax dosing duration across cycles, particularly after achieving remission, as excessive continuous dosing can cause problematic myelosuppression. Pharmacokinetic analysis showed no significant drug interactions between venetoclax and oral decitabine.
This all-oral regimen represents a potential paradigm shift in AML management, offering significant advantages in patient convenience and clinic resource utilization. The therapy could become a new standard of care for older, unfit patients with AML, with regulatory submission planned for 2026 approval consideration. The oral backbone provides opportunities for combination with additional oral agents, including IDH inhibitors, FLT3 inhibitors, and potentially menin inhibitors, potentially leading to improved outcomes while maintaining the convenience of home-based treatment for this patient population requiring palliative care approaches.
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