Quality-adjusted Time Without Symptoms of disease or Toxicity (Q-TWiST) analysis of CPX-351 versus 7 + 3 in older adults with newly diagnosed high-risk/secondary AML

Journal of Hematology & Oncology

Jorge E. Cortes¹  Jeffrey E. Lancet²  Stefan Faderl³  Robert J. Ryan⁴  Tara L. Lin⁵  Geoffrey L. Uy⁶ 

[1] Georgia Cancer Center, Augusta University, 1410 Laney Walker Rd., CN2116, 30912, Augusta, GA, USA;H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA;Jazz Pharmaceuticals, Palo Alto, CA, USA;Jazz Pharmaceuticals, Philadelphia, PA, USA;University of Kansas Medical Center, Kansas City, KS, USA;Washington University School of Medicine, St. Louis, MO, USA;

关键词: Acute myeloid leukemia;    Chemotherapy;    Relapse;    Survival;    Toxicity;    Quality-of-life;   

DOI  :  10.1186/s13045-021-01119-w

来源: Springer

【 摘 要 】

BackgroundCPX-351 (United States: Vyxeos®; Europe: Vyxeos® Liposomal), a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, is approved by the US FDA and the EMA for the treatment of adults with newly diagnosed therapy-related acute myeloid leukemia or acute myeloid leukemia with myelodysplasia-related changes. In a pivotal phase 3 study that evaluated 309 patients aged 60 to 75 years with newly diagnosed high-risk/secondary acute myeloid leukemia, CPX-351 significantly improved median overall survival versus conventional 7 + 3 chemotherapy (cytarabine continuous infusion for 7 days plus daunorubicin for 3 days), with a comparable safety profile. A Quality‐adjusted Time Without Symptoms of disease or Toxicity (Q-TWiST) analysis of the phase 3 study was performed to compare survival quality between patients receiving CPX-351 versus conventional 7 + 3 after 5 years of follow-up.MethodsPatients were randomized 1:1 between December 20, 2012 and November 11, 2014 to receive induction with CPX-351 or 7 + 3. Survival time for each patient was partitioned into 3 health states: TOX (time with any grade 3 or 4 toxicity or prior to remission), TWiST (time in remission without relapse or grade 3 or 4 toxicity), and REL (time after relapse). Within each treatment arm, Q-TWiST was calculated by adding the mean time spent in each health state weighted by its respective quality-of-life, represented by health utility. The relative Q-TWiST gain, calculated as the difference in Q-TWiST between treatment arms divided by the mean survival of the 7 + 3 control arm, was determined in order to evaluate results in the context of other Q-TWiST analyses.ResultsThe relative Q-TWiST gain with CPX-351 versus 7 + 3 was 53.6% in the base case scenario and 39.8% among responding patients. Across various sensitivity analyses, the relative Q-TWiST gains for CPX-351 ranged from 48.0 to 57.6%, remaining well above the standard clinically important difference threshold of 15% for oncology.ConclusionsThis post hoc analysis demonstrates that CPX-351 improved quality-adjusted survival, further supporting the clinical benefit in patients with newly diagnosed high-risk/secondary acute myeloid leukemia.Trial registration This trial was registered on September 28, 2012 at www.clinicaltrials.gov as NCT01696084 (https://clinicaltrials.gov/ct2/show/NCT01696084) and is complete.

【 授权许可】

CC BY