Portal de Periódicos da CAPES

Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML.

2016; Lippincott Williams & Wilkins; Volume: 34; Issue: 15_suppl Linguagem: Inglês

10.1200/jco.2016.34.15_suppl.7000

1527-7755

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

Protein Degradation and Inhibitors

7000 Background: Older patients with secondary AML have poor outcomes following first-line cytarabine and anthracycline-based treatment. CPX-351 is a liposomal formulation of cytarabine and daunorubicin encapsulated at a 5:1 molar ratio with enhanced efficacy among poor risk AML patients. We report final results from a randomized open-label study of first-line CPX-351 in patients with high-risk sAML (NCT01696084). Methods: Patients 60-75 years of age with untreated AML with a history of prior cytotoxic treatment, antecedent MDS or CMML (+/- prior hypomethylator treatment), or AML with WHO-defined MDS-related cytogenetic abnormalities were eligible. 300 patients were to be randomized 1:1 to CPX-351 (100 units/m2, days 1, 3, 5) or 7+3 (cytarabine 100 mg/m2/day x 7 days, daunorubicin 60 mg/m2 days 1, 2, 3) induction therapy. Endpoints included: overall (OS, 1o) and event free survival (EFS) assessed by stratified log rank analysis, independent blinded assessment of CR+CRi, and 60-day mortality. Patient enrollment was from Dec 2012 to Nov 2014 at 39 US and Canadian sites. Study assumptions included: exponential survival, control median OS=192d, accrual of 135 pt/yr, and analysis after 236 deaths, resulting in 93.7% power to detect a HR=0.635, p=0.05 (2-sided). Results: A total of 309 patients were randomized (153 to CPX-351 + 156 to 7+3) and were well balanced for sex, race, age, performance status, AML-subtype, MDS-related cytogenetics and prior HMA therapy. After minimum follow-up of 13.7 months final analysis began.CPX-351 treatment resulted in superior overall survival (HR=0.69; P=0.005; median OS 9.56 vs. 5.95 months), EFS (HR=0.74; P=0.021), and CR+CRi response (47.7% vs. 33.3%; P=0.016). 60-day mortality favored CPX-351 (13.7% vs. 21.2%). Grade 3-5 AEs were equal (92% vs. 91%) and were similar in frequency and severity in both arms. Similar numbers of patients were transplanted in both arms. Conclusion: CPX-351 treatment significantly improved overall survival, event free survival, and response without an increase in 60-day mortality or AE frequency or severity. CPX-351 should become the standard of care for older patients with secondary AML. Clinical trial information: NCT01696084.