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

© 2021. The Author(s)..

BACKGROUND: CPX-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.

METHODS: Patients 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.

RESULTS: The 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.

CONCLUSIONS: This 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.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:14

Enthalten in:

Journal of hematology & oncology - 14(2021), 1 vom: 13. Juli, Seite 110

Sprache:

Englisch

Beteiligte Personen:

Cortes, Jorge E [VerfasserIn]
Lin, Tara L [VerfasserIn]
Uy, Geoffrey L [VerfasserIn]
Ryan, Robert J [VerfasserIn]
Faderl, Stefan [VerfasserIn]
Lancet, Jeffrey E [VerfasserIn]

Links:

Volltext

Themen:

04079A1RDZ
Acute myeloid leukemia
Antineoplastic Agents
CPX-351
Chemotherapy
Clinical Trial, Phase III
Cytarabine
Daunorubicin
Journal Article
Multicenter Study
Quality-of-life
Randomized Controlled Trial
Relapse
Research Support, Non-U.S. Gov't
Survival
Toxicity
ZS7284E0ZP

Anmerkungen:

Date Completed 01.11.2021

Date Revised 01.11.2021

published: Electronic

ClinicalTrials.gov: NCT01696084

Citation Status MEDLINE

doi:

10.1186/s13045-021-01119-w

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM328025011