1. A systematic review of higher-risk myelodysplastic syndromes clinical trials to determine the benchmark of azacitidine and explore alternative endpoints for overall survival.
- Author
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Garcia JS, Swords RT, Roboz GJ, Jacoby MA, Garcia-Manero G, Hong WJ, Yang X, Zhou Y, Platzbecker U, Steensma DP, Wolff JE, and Fenaux P
- Subjects
- Antimetabolites, Antineoplastic adverse effects, Azacitidine adverse effects, Clinical Trials as Topic, Disease-Free Survival, Humans, Survival Rate, Antimetabolites, Antineoplastic therapeutic use, Azacitidine therapeutic use, Myelodysplastic Syndromes drug therapy, Myelodysplastic Syndromes mortality
- Abstract
The hypomethylating agent azacitidine can prolong overall survival (OS) in patients with higher risk-myelodysplastic syndromes (HR-MDS) compared to conventional regimens. However, outcomes differ largely between studies, making it challenging to determine the contribution of novel therapies added to azacitidine. Further, a discrepancy is seen between complete (CR) or partial (PR) response rates and OS improvement with azacitidine, making it challenging to rely on earlier endpoints than OS. We conducted a systematic literature search and study-level systematic review of 237 clinical studies to better understand outcomes for HR-MDS patients treated with azacitidine. Pooled marrow CR was 9% (N = 2654; 95% CI: 6-13 %), CR rate was 17 % (N = 6943; 95% CI: 15-20 %), and median OS (mOS) was 18.6 months (N = 2820; 95% CI: 15.3-21.9). A weak correlation to mOS was detected with CR rate (207 patient cohorts, Pearson's r = 0.315; P < 0.0005), and a much stronger correlation with median progression-free survival (mPFS) (r=0.88, P = 3 × 10
-14 ). Six-months progression-free survival rates correlated with 1-year OS rates but were only infrequently reported (N = 41 patient cohorts) therefore not allowing a robust recommendation for a surrogate to the established OS endpoint. Larger patient numbers and patient-level data appear necessary, especially for designing future clinical trials using azacitidine combinations., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2021
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