1. CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia
- Author
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Lancet, Jeffrey E, Uy, Geoffrey L, Cortes, Jorge E, Newell, Laura F, 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, and Medeiros, Bruno C
- Subjects
Orphan Drug ,Clinical Trials and Supportive Activities ,Hematology ,Pediatric ,Cancer ,Rare Diseases ,Clinical Research ,Pediatric Cancer ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Aged ,Antineoplastic Combined Chemotherapy Protocols ,Cytarabine ,Daunorubicin ,Female ,Humans ,Leukemia ,Myeloid ,Acute ,Male ,Middle Aged ,Neoplasms ,Second Primary ,Clinical Sciences ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - 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.
- Published
- 2018