DACO-016: trial | Bending the Curve: Trial by Trial

DACO-016

Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia

Phase 3N = 485NCT00260832

Population

Newly diagnosed AML, age 65 years or older, with poor- or intermediate-risk cytogenetics

Design

Multicenter randomized (1:1), open-label phase 3 trial. Decitabine 20 mg/m2 per day as a 1-hour infusion for 5 consecutive days every 4 weeks, or treatment choice (supportive care or cytarabine 20 mg/m2 per day subcutaneously for 10 consecutive days every 4 weeks). Primary end point: overall survival; secondary: CR rate plus CR without platelet recovery (CRp).

Primary endpoint

Arms

Decitabine (experimental, n = 242): Decitabine 20 mg/m2 per day for 5 consecutive days every 4 weeks
Treatment choice (control, n = 243): Patient choice, with physician advice, of supportive care or cytarabine 20 mg/m2 per day subcutaneously for 10 days every 4 weeks

People

Kantarjian HM

OSHR 0.85 (95% CI 0.69–1.04)Δ median OS+2.7 monthsOSHR 0.82 (95% CI 0.68–0.99)Δ CR+CRp+10 points

Show the numbers

Results reported for DACO-016
Endpoint	Analysis	Decitabine	Treatment choice	Effect
OSITT (all randomly assigned patients, N = 485)	primaryKantarjian 2012	median 7.7 months (6.2–9.2)	median 5 months (4.3–6.3)	HR 0.85 (95% CI 0.69–1.04)P=.108Nonsignificant in the primary analysis, as the abstract states.
OSITT (all randomly assigned patients, N = 485)	exploratoryKantarjian 2012	—	—	HR 0.82 (95% CI 0.68–0.99)P=.037 (nominal)Unplanned analysis with 446 deaths (92%); the abstract states the median OS was the same as in the primary analysis.
CR+CRpITT (all randomly assigned patients, N = 485)Complete remission rate plus complete remission without platelet recovery (CRp)	primaryKantarjian 2012	17.8%	7.8%	P=.001Odds ratio 2.5 (95% CI 1.4 to 4.8). Secondary end point.

Results reported for DACO-016
Endpoint	Analysis	Decitabine	Treatment choice	Effect
OSITT (all randomly assigned patients, N = 485)	primaryKantarjian 2012	median 7.7 months (6.2–9.2)	median 5 months (4.3–6.3)	HR 0.85 (95% CI 0.69–1.04)P=.108Nonsignificant in the primary analysis, as the abstract states.
OSITT (all randomly assigned patients, N = 485)	exploratoryKantarjian 2012	—	—	HR 0.82 (95% CI 0.68–0.99)P=.037 (nominal)Unplanned analysis with 446 deaths (92%); the abstract states the median OS was the same as in the primary analysis.
CR+CRpITT (all randomly assigned patients, N = 485)Complete remission rate plus complete remission without platelet recovery (CRp)	primaryKantarjian 2012	17.8%	7.8%	P=.001Odds ratio 2.5 (95% CI 1.4 to 4.8). Secondary end point.

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
OS	0.85	0.69–1.04
OS	0.82	0.68–0.99

Illustrative — modelled from reported values, not trial data. OS, primary.

Show curves

Decitabine (experimental)
Treatment choice (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Decitabine	Treatment choice
0	100.0%	100.0%
5	63.8%	50.0%
10	40.6%	25.0%
14	28.4%	14.4%
19	18.1%	7.2%

Appears in

2009 Azacitidine and decitabine in older adults with AML

Sources

Kantarjian HM, Thomas XG, Dmoszynska A, Wierzbowska A, Mazur G, Mayer J, et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012;30(21):2670-7.
PubMed DOI