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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

ONUREG® Circles

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

1:1 randomization
(N=472)
TREATMENT PHASE
Key inclusion criteria*:
  • 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.

ONUREG® (n=238) 300 mg orally once daily, Days 1‑14 of each 28‑day treatment cycle
Placebo (n=234) Orally once daily, Days 1‑14 of each 28‑day treatment cycle
Continue treatment
until disease progression
or unacceptable toxicity

In the trial, eligible patients were enrolled regardless of mutational status.3

In the trial, prophylactic therapy for gastrointestinal (GI) or hematologic adverse events was not mandated; best supportive care was permitted at the discretion of the treating investigator4
Based on the full Prescribing Information, patients should take an antiemetic 30 minutes prior to each dose of ONUREG® for the first 2 cycles1

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)

72% of patients were 65 years or older
Included patients with NPM1 mutation (ONUREG® [n=66] vs placebo [n=71])5
Time from CR/Ci to enrollment ranged from 1.4 to 8.8 months for patients treated with ONUREG®4

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

ONUREG® 73 (n=168)
(95% CI: 67, 78)
Placebo 56 (n=127)
(95% CI: 49, 62)

2 years

ONUREG® 51 (n=115)
(95% CI: 44, 57)
Placebo 37 (n=82)
(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

ONUREG® Primary Endpoint by Subgroup Chart

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.

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