Overall survival is more than double at 5 years with VYXEOS (18%) vs 7+3 (8%) based on KM estimates1,2
Median overall survival (primary analysis) of 9.6 months with VYXEOS vs 5.9 months with 7+3, reducing the risk of death by 31% (HR=0.69 [95% CI: 0.52, 0.90], P=0.005a)1
Kaplan-Meier curve for overall survival, ITT population2
Reprinted from Lancet JE, et al. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021;8(7):e481-e491, with permission from Elsevier.
This prospectively planned overall survival analysis of the ITT population was conducted based on the final 5-year follow-up results from the Phase 3 trial2
aP value is 2-sided.1
Exploratory post hoc analysis
At 5 years, median overall survival was longer with VYXEOS vs 7+3 in patients aged 60-69 and 70-75 years2
5-YEAR FOLLOW-UP
Kaplan-Meier curve for overall survival by age subgroup, aged 60 to 69 years4
Median overall survival (95% CI):
VYXEOS: 9.6 months (6.0, 12.6) (n=76/96)
7+3: 6.9 months (4.6, 8.8) (n=91/102)
Reprinted from Lancet JE, et al. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021;8(7):e481-e491, with permission from Elsevier.
Age was prospectively stratified in the initial analysis of the Phase 3 trial2
See the Phase 3 Study Safety Profile
Limitations of subanalysis
- This exploratory post hoc subgroup analysis was not powered to determine statistical significance. No efficacy conclusions about OS can be drawn from this analysis
Kaplan-Meier curve for overall survival by age subgroup, aged 70 to 75 years4
Median overall survival (95% CI):
VYXEOS: 8.9 months (4.7, 12.2) (n=48/57)
7+3: 5.6 months (3.3, 7.5) (n=54/54)
Reprinted from Lancet JE, et al. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021;8(7):e481-e491, with permission from Elsevier.
Age was prospectively stratified in the initial analysis of the Phase 3 trial2
See the Phase 3 Study Safety Profile
Limitations of subanalysis
- This exploratory post hoc subgroup analysis was not powered to determine statistical significance. No efficacy conclusions about OS can be drawn from this analysis
Strive for higher remission rates in sAML with VYXEOS1,3
In the Phase 3 trial, almost half of sAML patients treated with VYXEOS achieved CR+CRi3
Percentage of sAML patients who achieved CR and CR+CRi1,3
Exploratory post hoc analysis
At 5 years, median overall survival was longer in patients who achieved CR or CRi with VYXEOS vs 7+34
5-YEAR FOLLOW-UP
Kaplan-Meier curve for overall survival in patients who achieved CR or CRi4
Median overall survival (95% CI):
VYXEOS: 21.7 months (13.0, 29.7) (n=50/73)
7+3: 10.4 months (7.8, 15.2) (n=43/52)
Reprinted from Lancet JE, et al. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021;8(7):e481-e491, with permission from Elsevier.
Limitations of subanalysis
- This exploratory post hoc subgroup analysis was not powered to determine statistical significance. No efficacy conclusions about OS can be drawn from this analysis
- Results should be interpreted with caution, as this analysis was not prespecified and was conducted in a small, nonrandomized subgroup (n=125)2,4
- The treatment effect of this nonrandomized subgroup was possibly confounded by unbalanced baseline characteristics
For sAML patients whose treatment goals align with transplant, start with VYXEOS2
The foundation of sAML treatment is chemotherapy, with the ultimate goal of achieving remission and reaching HSCT6-8,f
- NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.
Exploratory post hoc analysis
Long-term OS in patients who received HSCT in the Phase 3 trial2
LONG-TERM FOLLOW-UP
Analysis 1: Kaplan-Meier curve for overall survival landmarked from time of HSCT2
Median overall survival (95% CI):
VYXEOS: Not reached (16.2, NR) (n=23/53)9
7+3: 10.3 months (6.2, 16.7) (n=30/39)9
Reprinted from Lancet JE, et al. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021;8(7):e481-e491, with permission from Elsevier.
5-year KM estimates from date of HSCT were not available, as the follow-up time from date of HSCT was less than 5 years2
KM-estimated survival rates from date of randomization were higher for VYXEOS vs 7+3 at 3 and 5 years and was >50% at 5 years for patients treated with VYXEOS10,11
Limitations of subanalysis
- This exploratory post hoc subgroup analysis was not powered to determine statistical significance. No efficacy conclusions about OS following HSCT can be drawn from this analysis
- Results should be interpreted with caution, as this analysis was not prespecified and was conducted in a small, nonrandomized subgroup (n=92)2
- The treatment effect of this nonrandomized subgroup was possibly confounded by unbalanced baseline characteristics
- A higher proportion of patients proceeding to HSCT in the VYXEOS arm (75%) were in CR/CRi as compared with the 7+3 arm (62%)2
- To address this limitation, Analysis 2 (right)(below) evaluated only those patients in each treatment arm who were in CR/CRi at the time they received HSCT4
Analysis 2: Kaplan-Meier curve for overall survival landmarked from time of HSCT in patients who achieved CR or CRi4
Median overall survival (95% CI):
VYXEOS: Not reached (15.6, NR) (n=19/41)
7+3: 11.7 months (4.6, 24.3) (n=17/24)
Reprinted from Lancet JE, et al. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021;8(7):e481-e491, with permission from Elsevier.
5-year KM estimates from date of HSCT were not available, as the follow-up time from date of HSCT was less than 5 years2
Limitations of subanalysis
- This exploratory post hoc subgroup analysis was not powered to determine statistical significance. No efficacy conclusions about OS following HSCT after CR or CRi can be drawn from this analysis
- Results should be interpreted with caution, as this analysis was not prespecified and was conducted in a small, nonrandomized subgroup (n=65)2,4
- The treatment effect of this nonrandomized subgroup was possibly confounded by unbalanced baseline characteristics
Exploratory post hoc analysis
Patients who achieved CR or CRi and did not undergo transplant in the Phase 3 trial12,g
Median OS for non-HSCT
patients who achieved CR12
Median OS for non-HSCT
patients who achieved CR+CRi12
Limitations of subanalysis
- This subgroup analysis was exploratory and not powered to determine statistical significance. No efficacy conclusions about OS following CR or CRi can be drawn from this analysis
- Results should be interpreted with caution, as this analysis was not prespecified and was conducted in a small, nonrandomized subgroup (n=61)12
- The treatment effect of this nonrandomized subgroup was possibly confounded by unbalanced baseline characteristics
gBased on primary analysis of median follow-up of 20.7 months.3
Study Design1,2
The Phase 3 study was a randomized, multicenter, open-label, active-controlled superiority study of VYXEOS (N=153) versus cytarabine and daunorubicin (7+3; N=156) in patients 60 to 75 years of age with newly-diagnosed t-AML or AML-MRC (N=309). Efficacy was established on the basis of overall survival from the date of randomization to death from any cause.1
VYXEOS 44 mg/100 mg per m2 (daunorubicin/cytarabine) was given intravenously on Days 1, 3, and 5 for first induction and on Days 1 and 3 for those needing a second induction. For consolidation, the VYXEOS dose was 29 mg/65 mg per m2 (daunorubicin/cytarabine) on Days 1 and 3. In the 7+3 arm, first induction was cytarabine 100 mg/m2/day on Days 1-7 by continuous infusion + daunorubicin 60 mg/m2/day on Days 1-3. For second induction and consolidation, cytarabine was dosed on Days 1-5 and daunorubicin on Days 1 and 2. Patients could receive up to 2 cycles of induction and 2 cycles of consolidation in each arm. Subsequent induction was highly recommended for patients who did not achieve a response and was mandatory for patients achieving >50% reduction in percent blasts.1
The prospectively planned overall survival analysis of the ITT population was conducted based on the final 5-year follow-up results from the Phase 3 trial. Exploratory post hoc subgroup analyses were also conducted.2