Phase 2, randomized, double‐blind study of pracinostat in combination with azacitidine in patients with untreated, higher‐risk myelodysplastic syndromes
Open accessAbstract
BACKGROUND: The prognosis of patients with higher‐risk myelodysplastic syndromes (MDS) remains poor despite available therapies. Histone deacetylase inhibitors have demonstrated activity in patients with MDS and in vitro synergy with azacitidine. METHODS: A phase 2 randomized, placebo‐controlled clinical trial of azacitidine and pracinostat was conducted in patients who had International Prognostic Scoring System intermediate‐2–risk or high‐risk MDS. The primary endpoint was the complete response (CR) rate by cycle 6 of therapy. RESULTS: Of 102 randomized patients, there were 51 in the pracinostat group and 51 in the placebo group. The median age was 69 years. The CR rate by cycle 6 of therapy was 18% and 33% (P = .07) in the pracinostat and placebo groups, respectively. No significant differences in overall survival (median, 16 vs 19 months, respectively; hazard ratio, 1.21; 95% confidence interval, 0.66‐2.23) or progression‐free survival (11 vs 9 months, respectively; hazard ratio, 0.82; 95% confidence interval, 0.546‐1.46) were observed between groups. Grade ≥3 adverse events occurred more frequently in the pracinostat group (98% vs 74%), leading to more treatment discontinuations (20% vs 10%). CONCLUSIONS: The combination of azacitidine with pracinostat did not improve outcomes in patients with higher‐risk MDS. Higher rates of treatment discontinuation may partially explain these results, suggesting alternative dosing and schedules to improve tolerability may be required to determine the potential of the combination. Cancer 2017;123:994–1002. © 2016 American Cancer Society.
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AZA alone continues to represent standard of care in MDS because all recent studies have failed to improve median OS compared to monotherapy.
“AZA alone continues to represent the standard of care in MDS because all recent studies have failed to improve the median OS compared to monotherapy.”
From Long‐term follow‐up and combined Phase 2 results of eprenetapopt and azacitidine in patients with <i>TP53</i> mutant MDS/AML (2025) · cites this paper as [35]
The Introduction identifies azacitidine or decitabine as standard-of-care therapies for higher-risk MDS. The Results (Survival; page unavailable) report median overall survival of 16 months with pracinostat plus azacitidine versus 19 months with azacitidine plus placebo, and the Discussion says the combination did not improve overall survival. The paper does not establish that all recent studies failed to improve median overall survival, or extend its finding to MDS generally. (LLM, conf=0.90)
Experimental — accuracy not yet measuredCombination therapies in MDS including HDAC inhibitors, lenalidomide, pevonedistat, and anthracyclines have not improved results.
“Combination therapies in this setting have included HDAC inhibitors, 33 , 34 , 35 lenalidomide, 36 pevonedistat, 37 and anthracyclines 38 all without improved results.”
From Long‐term follow‐up and combined Phase 2 results of eprenetapopt and azacitidine in patients with <i>TP53</i> mutant MDS/AML (2025) · cites this paper as [35]
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“Combination therapies in this setting have included HDAC inhibitors, 33 – 35 lenalidomide, 36 pevonedistat, 37 and anthracyclines 38 all without improved results.”
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- Authors
- Garcia‐Manero, G., Montalban‐Bravo, G., Berdeja, J. G., Abaza, Y., Jabbour, E., Essell, J., Lyons, R. M., Ravandi, F., Maris, M., Heller, B., DeZern, A. E., Babu, S., Wright, D., Anz, B., Boccia, R., Komrokji, R. S., Kuriakose, P., Reeves, J., Sekeres, M. A., Kantarjian, H. M., Ghalie, R., & Roboz, G. J.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas
- Sarah Cannon Research Institute Nashville Tennessee
- Oncology Hematology Care (US)
- Cancer Care Center of South Texas San Antonio Texas
- Colorado Blood Cancer Institute (US)
- Southern Cancer Center Daphne Alabama
- Johns Hopkins University (US)
- Fort Wayne Medical Institute (US)
- Florida Cancer Specialists‐North Jacksonville Florida
- Tennessee Oncology (US)
- Center for Cancers and Blood Disorders (US)
- Moffitt Cancer Center (US)
- Henry Ford Hospital (US)
- Florida Cancer Specialists‐South Cape Coral Florida
- Cleveland Clinic (US)
- MEI Pharma (United States) (US)
- Weill Cornell Medicine (US)
- Corresponding author
- Garcia‐Manero, Guillermo
- ORCID
- Venue
- Cancer
- Publisher
- Wiley
- Published
- 2017-01-17
- Volume
- 123
- Issue
- 6
- Pages
- 994-1002
- ISSN
- 0008-543X (ISSN-L)
- 1097-0142
- PMC
- PMC5432122
- OpenAlex
- W2574794018
- Cited by
- 104
- References
- 32
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 7 · 2023: 6 · 2022: 8 · 2021: 9 · 2020: 13 · 2019: 21 · 2018: 19 · 2017: 10
- FWCI
- 13.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Edward P. Evans Foundation
- MEI Pharma
- University of Texas MD Anderson Cancer Center ((CA016672), P30-CA-016672)
- National Cancer Institute (P30CA016672)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Keywords
- pracinostat, azacitidine, myelodysplastic syndrome, high-risk MDS, histone deacetylase inhibitors, combination therapy, complete response, treatment discontinuation, adverse events, progression-free survival, overall survival
- MeSH terms
- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Azacitidine, Benzimidazoles, Female, Humans, Male, Middle Aged, Myelodysplastic Syndromes, Prognosis, Biomarkers, Treatment Outcome, Disease Progression, Kaplan-Meier Estimate
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