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In newly-diagnosed secondary AML patients, VYXEOS demonstrated superior overall survival, higher CR and CR+CRi rates, and a better chance to reach HSCT vs 7+31,2,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

VYXEOS demonstrated superior overall survival vs 7+3, reducing the risk of death by 31%b in sAML patients facing a poor prognosis (primary endpoint)1

Kaplan-Meier curve for overall survival, ITT population1

VYXEOS demonstrated a statistically significant improvement in CR and CR+CRi vs 7+31,2

Percentage of sAML patients who achieved CR and CR+CRi1,2

OS in sAML patients who achieved CR or CRi4

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

OS in sAML patients who achieved CR or CRi4

Limitations of subanalysis4

  • Results should be interpreted with caution, as this was an exploratory analysis of a specific subgroup
  • The treatment effect of this nonrandomized subgroup was possibly confounded by unbalanced baseline characteristics
  • This analysis was potentially biased, as it included only responders who achieved CR or CRi
  • Of the patients who achieved CR or CRi, 55% of patients in the VYXEOS arm underwent HSCT (n=40/73) compared to 46% of patients in the 7+3 arm (n=24/52)

Chemotherapy followed by HSCT provides an opportunity for prolonged survival5

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,e

OS from time of HSCT after treatment with VYXEOS

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

OS in from time of HSCT in CR/CRi patients who received VYXEOS

Median survival (95% CI)

VYXEOS: (n=13/39) Not reached (15.6, NR)
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 highly 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.