Efficacy
The large, multicenter QUAZAR® AML-001 trial established the efficacy and safety of the first and only FDA-approved continued treatment for AML1,2
The efficacy of ONUREG® was established on the basis of overall survival1
QUAZAR® AML-001 was designed to evaluate ONUREG® vs placebo
as
continued treatment for adult patients in first CR/CRi1
(N=472)
- Adults ≥55 years of age
- Diagnosed with AML
- Within 4 months of achieving first CR or CRi with intensive induction chemotherapy with or without consolidation therapy
*Not a comprehensive list of inclusion criteria.
until disease progression
or unacceptable toxicity
In the trial, eligible patients were enrolled regardless of mutational status.3
The QUAZAR® AML-001 trial enrolled a broad AML population1
Select baseline demographics and disease-related characteristics in the QUAZAR® AML-001 trial1
Parameter |
ONUREG®(n=238) |
Placebo(n=234) |
|---|---|---|
|
Age (years) |
||
|
Median (min, max) |
68.0 (55, 86) |
68.0 (55, 82) |
|
Age category, n (%) |
||
|
<65 years |
66 (28) |
68 (29) |
|
65 years to <75 years |
144 (61) |
142 (61) |
|
≥75 years |
28 (12) |
24 (10) |
|
ECOG performance status, n (%) |
||
|
0 |
116 (49) |
111 (47) |
|
1 |
101 (42) |
106 (45) |
|
2 |
21 (9) |
15 (6) |
|
3 |
0 (0) |
2 (1) |
|
Cytogenetic risk status at diagnosis, n (%) |
||
|
Intermediate risk1 |
203 (85) |
203 (87) |
|
Poor risk2 |
35 (15) |
31 (13) |
|
Initial AML classification, n (%) |
||
|
AML with recurrent genetic abnormalities |
39 (16) |
46 (20) |
|
AML with myelodysplasia-related changes |
49 (21) |
42 (18) |
|
Therapy-related myeloid neoplasms |
2 (1) |
0 (0) |
|
AML not otherwise specified |
148 (62) |
145 (62) |
|
Missing |
0 (0) |
1 (<1) |
|
Type of AML, n (%) |
||
|
Primary (de novo) |
213 (89) |
216 (92) |
|
Secondary |
25 (11) |
18 (8) |
|
Induction response |
||
|
CR |
187 (79) |
197 (84) |
|
CRi |
51 (21) |
37 (16) |
|
Received consolidation following induction therapy |
||
|
None |
52 (22) |
42 (18) |
|
1 cycle |
110 (46) |
102 (44) |
|
2 cycles |
70 (29) |
77 (33) |
|
3 cycles |
6 (3) |
13 (6) |
|
Time from induction therapy to randomization (months)3 |
||
|
Median (min, max) |
4.0 (1.4, 8.8) |
4.0 (1.3, 15.1) |
|
Disease status at study baseline |
||
|
CR |
185 (78) |
181 (77) |
|
CRi |
44 (18) |
38 (16) |
|
Not in CR or CRi |
9 (4) |
13 (6) |
|
Not reported |
0 |
2 (1) |
ECOG, Eastern Cooperative Oncology Group.
1Intermediate risk was defined as normal cytogenetics +8, t(9;11), or other undefined.
2Poor risk was defined as complex (≥3 abnormalities): -5; 5q-; -7; 7q-; 11q23 - non t(9;11); inv(3); t(3;3); t(6;9); or t(9;22).
3For this measure, ONUREG® (n=237) and placebo (n=232).
Source for Intermediate and Poor Risk: NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia. National Comprehensive Cancer Network® (NCCN®) website.
Available at http://www.nccn.org/professionals/physician_gls/PDF/aml.pdf. Accessed March 1, 2011.
ONUREG® demonstrated >2 years median overall survival for AML patients in first remission1
Kaplan-Meier curve for OS: ITT population in QUAZAR® AML-0011
~10 months
longer OS with ONUREG®
vs placebo
HR† 0.69 (95% CI: 0.55, 0.86; P=0.0009)
CI, confidence interval; ITT, intention-to-treat.
*ONUREG® (95% CI: 18.7, 30.5); placebo (95% CI: 11.7, 17.6).
†The HR is from a Cox proportional hazards model stratified by age (55 to 64 vs ≥65 years), cytogenetic risk category at time of induction therapy (intermediate risk vs poor risk), and received consolidation therapy (yes vs no).
ONUREG® survival estimates
at 1 year and 2 years4
1 year
(95% CI: 67, 78)
(95% CI: 49, 62)
2 years
(95% CI: 44, 57)
(95% CI: 31, 43)
Analysis limitation
The analysis at these time points was not designed to show a difference between treatment arms.
Kaplan-Meier methods are used to estimate the 1-year and 2-year survival probabilities.
Primary endpoint subgroup analysis: treatment with ONUREG® across subgroups vs placebo for median overall survival4,6
OS select subgroup analysis
aNumber of events/number of subjects.
bMedian OS in months.
cPrior MDS and CMML.
Analysis limitations
These prespecified subgroup analyses should be interpreted with caution to determine a difference between arms in these select subgroups because of potential selection bias, insufficient sample size, and a higher probability of making a false positive finding.
ONUREG® overall survival for patients with an NPM1 mutation
The NPM1 mutation, which is prognostically favorable, occurs in ~30% of patients with AML (based on an analysis of 1540 AML patients from 3 prospective multicenter trials).7
QUAZAR® AML-001 retrospective, post hoc subgroup analysis5
28% (66/236) of patients who received ONUREG® and 30% (71/233) of patients who received placebo had an NPM1 mutation at diagnosis.
Analysis limitations
- Retrospective, exploratory, subgroup analyses of QUAZAR® AML-001 included an assessment of NPM1 mutation status at diagnosis and its impact on survival outcome
- These diagnostic analyses were obtained from local investigator reports and were not confirmed by central lab assessment. Of the 472 randomized patients, 469 were evaluable for the mutation
- This survival analysis should not be interpreted to determine a treatment difference between arms in these select endpoints because of potential selection bias, small sample size, and it was not statistically powered
Kaplan-Meier curve for OS: patients with an NPM1 mutation in QUAZAR® AML-0015*
Results should be interpreted with caution, as these cohorts were not prospectively defined, and the study was not powered to detect significant differences between subgroups.
*HR 0.63 (95% CI: 0.41, 0.98).8
†ONUREG® (95% CI: 34.3, NA); placebo (95% CI: 11.7, 44.1).8
NA, not available.