CHICAGO—In a Phase 3, multicenter trial involving patients ≥65 years who were newly diagnosed with de novo or secondary acute myeloid leukemia (AML), the cytosine nucleoside analog decitabine (DAC) demonstrated an overall survival advantage over standard therapies, including physician’s advice (treatment choice [TC]) of supportive care or low-dose cytarabine (AraC), according to data presented at the American Society of Clinical Oncology’s 2011 Annual Meeting.

Xavier G. Thomas, MD, from the Hospital Edouard Herriot, Lyon, France, and colleagues performed a randomized, controlled, open-label trial that enrolled 485 patients with poor- or intermediate-risk cytogenetics, and ECOG PS 0–2. They were randomized to either supportive care (n=28) or 20mg/m2 AraC SQ once daily for 10 consecutive days, every 4 weeks (n=215) or DAC 20mg/m2 as a 1-hour IV infusion once daily for 5 consecutive days, every 4 weeks (n=242). The primary endpoint was overall survival (OS). Additional endpoints were complete remission rates, safety, event-free survival, and relapse-free survival.

The results showed that patients randomized to DAC had a median duration of treatment of 4.4 months versus 2.4 months for those on the TC arm. The protocol-specified final analysis with 396 (81.6%) deaths showed a statistically nonsignificant but favorable trend for increased OS for patients treated with DAC, with a median survival of 7.7 months vs. 5.0 months in the TC arm; HR: 0.85, 95% CI [0.69–1.04]; P=0.108. When censored for disease modifying therapy, there was a significant improvement in OS for patients treated with DAC, with a median survival of 8.5 months vs. 5.3 months in the TC arm; HR: 0.80, 95% CI [0.64–0.99]; P=0.044.

An updated unplanned OS analysis with 446 (92%) deaths showed the same median survival with strengthened, albeit nominal evidence of the DAC effect (P=0.037) (0.82, 95%CI [0.68–0.99]). The secondary endpoint of complete remission (CR) + complete remission in the absence of total platelet recovery (CRp) rate was 17.8% (DAC) versus 7.8% (TC) with overall response (CR + CRp + partial response) of 2.5 (P=0.001). Safety rates were consistent with the known DAC safety profile and without major differences between the treatment arms. The most frequently reported Grade 3 or 4 hematologic adverse events were thrombocytopenia, anemia, neutropenia, and febrile neutropenia.