Cpx-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia

Jeffrey E. Lancet, Geoffrey L. Uy, Jorge E. Cortes, Laura Newell, Tara L. Lin, Ellen K. Ritchie, Robert K. Stuart, Stephen A. Strickland, Donna Hogge, Scott R. Solomon, Richard M. Stone, Dale L. Bixby, Jonathan E. Kolitz, Gary J. Schiller, Matthew J. Wieduwilt, Daniel H. Ryan, Antje Hoering, Kamalika Banerjee, Michael Chiarella, Arthur C. Louie & 1 others Bruno C. Medeiros

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Abstract

Purpose CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic 5:1 drug ratio into leukemia cells to a greater extent than normal bone marrow cells. Prior clinical studies demonstrated a sustained drug ratio and exposure in vivo and prolonged survival versus standard-of-care cytarabine plus daunorubicin chemotherapy (7+3 regimen) in older patients with newly diagnosed secondary acute myeloid leukemia (sAML). Patients and Methods In this open-label, randomized, phase III trial, 309 patients age 60 to 75 years with newly diagnosed high-risk/sAML received one to two induction cycles of CPX-351 or 7+3 followed by consolidation therapy with a similar regimen. The primary end point was overall survival. Results CPX-351 significantly improved median overall survival versus 7+3 (9.56 v 5.95 months; hazard ratio, 0.69; 95% CI, 0.52 to 0.90; one-sided P = .003). Overall remission rate was also significantly higher with CPX-351 versus 7+3 (47.7% v 33.3%; two-sided P = .016). Improved outcomes were observed across age-groups and AML subtypes. The incidences of nonhematologic adverse events were comparable between arms, despite a longer treatment phase and prolonged time to neutrophil and platelet count recovery with CPX-351. Early mortality rates with CPX-351 and 7+3 were 5.9% and 10.6% (two-sided P = .149) through day 30 and 13.7% and 21.2% (two-sided P = .097) through day 60. Conclusion CPX-351 treatment is associated with significantly longer survival compared with conventional 7+3 in older adults with newly diagnosed sAML. The safety profile of CPX-351 was similar to that of conventional 7+3 therapy.

Original languageEnglish (US)
Pages (from-to)2684-2692
Number of pages9
JournalJournal of Clinical Oncology
Volume36
Issue number26
DOIs
StatePublished - Sep 10 2018

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Daunorubicin
Cytarabine
Acute Myeloid Leukemia
Liposomes
Injections
Survival
Pharmaceutical Preparations
Therapeutics
Standard of Care
Platelet Count
Bone Marrow Cells
Leukemia
Neutrophils
Age Groups
Safety
Drug Therapy
Mortality
Incidence

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Cpx-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. / Lancet, Jeffrey E.; Uy, Geoffrey L.; Cortes, Jorge E.; Newell, Laura; Lin, Tara L.; Ritchie, Ellen K.; Stuart, Robert K.; Strickland, Stephen A.; Hogge, Donna; Solomon, Scott R.; Stone, Richard M.; Bixby, Dale L.; Kolitz, Jonathan E.; Schiller, Gary J.; Wieduwilt, Matthew J.; Ryan, Daniel H.; Hoering, Antje; Banerjee, Kamalika; Chiarella, Michael; Louie, Arthur C.; Medeiros, Bruno C.

In: Journal of Clinical Oncology, Vol. 36, No. 26, 10.09.2018, p. 2684-2692.

Research output: Contribution to journalArticle

Lancet, JE, Uy, GL, Cortes, JE, Newell, L, Lin, TL, Ritchie, EK, Stuart, RK, Strickland, SA, Hogge, D, Solomon, SR, Stone, RM, Bixby, DL, Kolitz, JE, Schiller, GJ, Wieduwilt, MJ, Ryan, DH, Hoering, A, Banerjee, K, Chiarella, M, Louie, AC & Medeiros, BC 2018, 'Cpx-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia', Journal of Clinical Oncology, vol. 36, no. 26, pp. 2684-2692. https://doi.org/10.1200/JCO.2017.77.6112
Lancet, Jeffrey E. ; Uy, Geoffrey L. ; Cortes, Jorge E. ; Newell, Laura ; Lin, Tara L. ; Ritchie, Ellen K. ; Stuart, Robert K. ; Strickland, Stephen A. ; Hogge, Donna ; Solomon, Scott R. ; Stone, Richard M. ; Bixby, Dale L. ; Kolitz, Jonathan E. ; Schiller, Gary J. ; Wieduwilt, Matthew J. ; Ryan, Daniel H. ; Hoering, Antje ; Banerjee, Kamalika ; Chiarella, Michael ; Louie, Arthur C. ; Medeiros, Bruno C. / Cpx-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 26. pp. 2684-2692.
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title = "Cpx-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia",
abstract = "Purpose CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic 5:1 drug ratio into leukemia cells to a greater extent than normal bone marrow cells. Prior clinical studies demonstrated a sustained drug ratio and exposure in vivo and prolonged survival versus standard-of-care cytarabine plus daunorubicin chemotherapy (7+3 regimen) in older patients with newly diagnosed secondary acute myeloid leukemia (sAML). Patients and Methods In this open-label, randomized, phase III trial, 309 patients age 60 to 75 years with newly diagnosed high-risk/sAML received one to two induction cycles of CPX-351 or 7+3 followed by consolidation therapy with a similar regimen. The primary end point was overall survival. Results CPX-351 significantly improved median overall survival versus 7+3 (9.56 v 5.95 months; hazard ratio, 0.69; 95{\%} CI, 0.52 to 0.90; one-sided P = .003). Overall remission rate was also significantly higher with CPX-351 versus 7+3 (47.7{\%} v 33.3{\%}; two-sided P = .016). Improved outcomes were observed across age-groups and AML subtypes. The incidences of nonhematologic adverse events were comparable between arms, despite a longer treatment phase and prolonged time to neutrophil and platelet count recovery with CPX-351. Early mortality rates with CPX-351 and 7+3 were 5.9{\%} and 10.6{\%} (two-sided P = .149) through day 30 and 13.7{\%} and 21.2{\%} (two-sided P = .097) through day 60. Conclusion CPX-351 treatment is associated with significantly longer survival compared with conventional 7+3 in older adults with newly diagnosed sAML. The safety profile of CPX-351 was similar to that of conventional 7+3 therapy.",
author = "Lancet, {Jeffrey E.} and Uy, {Geoffrey L.} and Cortes, {Jorge E.} and Laura Newell and Lin, {Tara L.} and Ritchie, {Ellen K.} and Stuart, {Robert K.} and Strickland, {Stephen A.} and Donna Hogge and Solomon, {Scott R.} and Stone, {Richard M.} and Bixby, {Dale L.} and Kolitz, {Jonathan E.} and Schiller, {Gary J.} and Wieduwilt, {Matthew J.} and Ryan, {Daniel H.} and Antje Hoering and Kamalika Banerjee and Michael Chiarella and Louie, {Arthur C.} and Medeiros, {Bruno C.}",
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TY - JOUR

T1 - Cpx-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia

AU - Lancet, Jeffrey E.

AU - Uy, Geoffrey L.

AU - Cortes, Jorge E.

AU - Newell, Laura

AU - Lin, Tara L.

AU - Ritchie, Ellen K.

AU - Stuart, Robert K.

AU - Strickland, Stephen A.

AU - Hogge, Donna

AU - Solomon, Scott R.

AU - Stone, Richard M.

AU - Bixby, Dale L.

AU - Kolitz, Jonathan E.

AU - Schiller, Gary J.

AU - Wieduwilt, Matthew J.

AU - Ryan, Daniel H.

AU - Hoering, Antje

AU - Banerjee, Kamalika

AU - Chiarella, Michael

AU - Louie, Arthur C.

AU - Medeiros, Bruno C.

PY - 2018/9/10

Y1 - 2018/9/10

N2 - Purpose CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic 5:1 drug ratio into leukemia cells to a greater extent than normal bone marrow cells. Prior clinical studies demonstrated a sustained drug ratio and exposure in vivo and prolonged survival versus standard-of-care cytarabine plus daunorubicin chemotherapy (7+3 regimen) in older patients with newly diagnosed secondary acute myeloid leukemia (sAML). Patients and Methods In this open-label, randomized, phase III trial, 309 patients age 60 to 75 years with newly diagnosed high-risk/sAML received one to two induction cycles of CPX-351 or 7+3 followed by consolidation therapy with a similar regimen. The primary end point was overall survival. Results CPX-351 significantly improved median overall survival versus 7+3 (9.56 v 5.95 months; hazard ratio, 0.69; 95% CI, 0.52 to 0.90; one-sided P = .003). Overall remission rate was also significantly higher with CPX-351 versus 7+3 (47.7% v 33.3%; two-sided P = .016). Improved outcomes were observed across age-groups and AML subtypes. The incidences of nonhematologic adverse events were comparable between arms, despite a longer treatment phase and prolonged time to neutrophil and platelet count recovery with CPX-351. Early mortality rates with CPX-351 and 7+3 were 5.9% and 10.6% (two-sided P = .149) through day 30 and 13.7% and 21.2% (two-sided P = .097) through day 60. Conclusion CPX-351 treatment is associated with significantly longer survival compared with conventional 7+3 in older adults with newly diagnosed sAML. The safety profile of CPX-351 was similar to that of conventional 7+3 therapy.

AB - Purpose CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic 5:1 drug ratio into leukemia cells to a greater extent than normal bone marrow cells. Prior clinical studies demonstrated a sustained drug ratio and exposure in vivo and prolonged survival versus standard-of-care cytarabine plus daunorubicin chemotherapy (7+3 regimen) in older patients with newly diagnosed secondary acute myeloid leukemia (sAML). Patients and Methods In this open-label, randomized, phase III trial, 309 patients age 60 to 75 years with newly diagnosed high-risk/sAML received one to two induction cycles of CPX-351 or 7+3 followed by consolidation therapy with a similar regimen. The primary end point was overall survival. Results CPX-351 significantly improved median overall survival versus 7+3 (9.56 v 5.95 months; hazard ratio, 0.69; 95% CI, 0.52 to 0.90; one-sided P = .003). Overall remission rate was also significantly higher with CPX-351 versus 7+3 (47.7% v 33.3%; two-sided P = .016). Improved outcomes were observed across age-groups and AML subtypes. The incidences of nonhematologic adverse events were comparable between arms, despite a longer treatment phase and prolonged time to neutrophil and platelet count recovery with CPX-351. Early mortality rates with CPX-351 and 7+3 were 5.9% and 10.6% (two-sided P = .149) through day 30 and 13.7% and 21.2% (two-sided P = .097) through day 60. Conclusion CPX-351 treatment is associated with significantly longer survival compared with conventional 7+3 in older adults with newly diagnosed sAML. The safety profile of CPX-351 was similar to that of conventional 7+3 therapy.

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U2 - 10.1200/JCO.2017.77.6112

DO - 10.1200/JCO.2017.77.6112

M3 - Article

VL - 36

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JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

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