All-Oral Decitabine/Cedazuridine Combo Enters Frontline AML

Following a Frontline Forum program, Amer Zeidan, MBBS, MD, discussed the May 2026 FDA approval of all-oral decitabine/cedazuridine (DEC-C; Inqovi) plus venetoclax (Venclexta) for newly diagnosed acute myeloid leukemia (AML) and how quickly it may replace injectable hypomethylating agent (HMA) combinations.¹ The approval was based on the phase 2 ASCERTAIN-V trial (NCT04657081).²

Topline data at the time of the approval showed that DEC-C plus venetoclax produced complete responses (CRs) in 41.6% (n = 42/101; 95% CI, 31.9%-51.8%) of evaluable patients. The median time to CR was 2 months (range, 0.4-15.3), and the median duration of CR was not reached (range, 0.5-16.3).

Zeidan said the data show comparable efficacy and safety relative to injectable azacitidine, making it reasonable to start patients on oral therapy or switch those already receiving injectable HMAs. He also emphasized the continued need to reinforce adherence and monitoring.

Zeidan is a professor of medicine at Yale School of Medicine and chief of the Division of Hematologic Malignancies, director of Hematology Early Therapeutics Research, and assistant director of the Clinical Trial Office for Hematology at Yale Comprehensive Cancer Center in New Haven, Connecticut.

Transcript:

CancerNetwork^®: Given the May 2026 FDA approval of oral DEC-C plus venetoclax based on the ASCERTAIN-V data, how quickly do you see this all-oral regimen replacing traditional intravenous/subcutaneous HMA combinations?

Zeidan: The ASCERTAIN-V data clearly showed comparable efficacy and safety for the all-oral approach of oral decitabine/cedazuridine plus venetoclax relative to the injectable form of azacitidine. [I]t’s very reasonable to consider starting patients on oral therapy or switching patients already receiving injectable HMAs to oral HMAs. There are certain features that might make someone not do this, such as poor compliance, social barriers to coming to the clinic, or financial problems. But for the vast majority of patients, this is a very reasonable approach to consider. You [must] emphasize compliance and monitor the patient the same way you would with the injectable form.

References

1. Zeidan AM, Griffiths EA, Dinardo CD, et al. An all-oral regimen of decitabine-cedazuridine (DEC-C) plus venetoclax in patients with newly diagnosed AML ineligible for intensive induction chemotherapy: results from a phase 2 cohort of 101 patients. J Clin Oncol. 2025;43(suppl 16):6504. doi:10.1200/JCO.2025.43.16_suppl.6504
2. FDA approves oral combination of decitabine and cedazuridine tablets with venetoclax for newly diagnosed acute myeloid leukemia. News release. FDA. May 13, 2026. Accessed July 1, 2026. https://tinyurl.com/ykk7yhfz