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VYXEOS demonstrated superior overall survival and higher HSCT rates vs 7+31,a

Discussion of the pivotal Phase 3 trial

Dr. Bayard Powell, section chief of Hematology and Oncology at Wake Forest Baptist Health, reviews the VYXEOS Phase 3 trial in detail and explains what the efficacy and safety data mean for adult sAML patients

Results of the Phase 3 trial were also published in the Journal of Clinical Oncology2

Overall survival

Kaplan-Meier curve for overall survival, ITT population1

Prespecified exploratory subgroup analysis of overall survival by age in the Phase 3 trial2

Limitations of subanalysis2

  • Results should be interpreted with caution, as this is an exploratory analysis of a specific subgroup

Patients receiving consolidation following successful induction had longer overall survival with VYXEOS vs those receiving 7+3/5+23,b

Outcomes in an exploratory post hoc analysis using data from the Phase 3 trial3

Limitations of subanalysis3

  • Results should be interpreted with caution, as this is an exploratory analysis of a specific subgroup
  • This analysis is potentially biased as it only includes responders who went on to receive consolidationc
  • The treatment effect of this nonrandomized subgroup is possibly confounded by unbalanced baseline characteristics

Overall response

Percentage of patients who achieved CR and CR+CRi1,4

Rate of HSCT

Prespecified exploratory subgroup analysis of transplant rate by age in the Phase 3 trial6

Limitations of subanalysis6

  • Results should be interpreted with caution, as this is an exploratory analysis of a specific subgroup
  • This analysis was limited by the small patient number and that no statistical analysis was conducted on rate of HSCT by age group

Exploratory post hoc analyses of overall survival following HSCT in the Phase 3 trial

These subgroup analyses were exploratory and not powered to determine statistical significance. No efficacy conclusions about OS following HSCT can be drawn from these analyses

Analysis 1: Kaplan-Meier curve for OS landmarked from time of transplant, ITT population2,f

Kaplan-Meier curve for overall survival following HSCT with VYXEOS (daunorubicin and cytarabine) vs 7+3

Median survival (95% CI)

VYXEOS: (n=18/52) Not reached
7+3: (n=26/39) 10.3 months (6.2, 16.7)

Limitations of subanalysis

  • Results should be interpreted with caution, as this analysis was not prespecified and was conducted in a small, nonrandomized subgroup (n=91)2,7
  • 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%)7
    • 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 HSCT8

Analysis 2: Kaplan-Meier curve for OS landmarked from time of transplant in patients in CR/CRi at time of HSCT8

Kaplan-Meier curve for overall survival following HSCT in patients in CR/CRi at time of HSCT with VYXEOS (daunorubicin and cytarabine) vs 7+3

Median survival (95% CI)

VYXEOS: (n=13/39) Not reached (15.6, not reached)
7+3: (n=16/24) 11.7 months (4.6, 24.3)

Limitations of subanalysis

  • Results should be interpreted with caution, as this analysis was not prespecified and was conducted in a small, nonrandomized subgroup (n=63)8
  • The treatment effect of this nonrandomized subgroup was possibly confounded by unbalanced baseline characteristics

Study Design1

The Phase 3 study was a randomized, multicenter, open-label, active-controlled superiority study of VYXEOS versus cytarabine and daunorubicin (7+3) in patients 60 to 75 years of age with newly-diagnosed t-AML or AML-MRC. There were 153 patients randomized to VYXEOS and 156 patients randomized to the 7+3 arm. Twenty percent had t-AML, 54% had AML with an antecedent hematological disorder, and 25% had de novo AML with MDS-related cytogenetic abnormalities. Efficacy was established on the basis of overall survival from the date of randomization to death from any cause.

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 recommended for patients who did not achieve a response and was mandatory for patients achieving >50% reduction in percent blasts.

Learn more about the Phase 3 study design

INDICATION

VYXEOS (daunorubicin and cytarabine) liposome for injection 44 mg/100 mg is indicated for the treatment of adults with newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC).

IMPORTANT SAFETY INFORMATION

INDICATION

VYXEOS (daunorubicin and cytarabine) liposome for injection 44 mg/100 mg is indicated for the treatment of adults with newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC).

Important Safety Information

WARNING: DO NOT INTERCHANGE WITH OTHER DAUNORUBICIN AND/OR CYTARABINE-CONTAINING PRODUCTS

VYXEOS has different dosage recommendations than daunorubicin hydrochloride injection, cytarabine injection, daunorubicin citrate liposome injection, and cytarabine liposome injection. Verify drug name and dose prior to preparation and administration to avoid dosing errors.