title: Phase 2, randomized, double-blind study of pracinostat in combination with azacitidine in patients with untreated, higher-risk myelodysplastic syndromes.
abstract: 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.
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Montalban-Bravo
authors.affiliation: Sarah Cannon Research Institute, Nashville, Tennessee.
authors.forename: Jesus G
authors.initials: JG
authors.lastname: Berdeja
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Abaza
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.affiliation: Oncology/Hematology Care, Cincinnati, Ohio.
authors.forename: James
authors.initials: J
authors.lastname: Essell
authors.affiliation: Cancer Care Center of South Texas, San Antonio, Texas.
authors.forename: Roger M
authors.initials: RM
authors.lastname: Lyons
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.affiliation: Colorado Blood Cancer Institute, Denver, Colorado.
authors.forename: Michael
authors.initials: M
authors.lastname: Maris
authors.affiliation: Southern Cancer Center, Daphne, Alabama.
authors.forename: Brian
authors.initials: B
authors.lastname: Heller
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Amy E
authors.initials: AE
authors.lastname: DeZern
authors.affiliation: Fort Wayne Medical Oncology and Hematology, Fort Wain, Indiana.
authors.forename: Sunil
authors.initials: S
authors.lastname: Babu
authors.affiliation: Florida Cancer Specialists-North, Jacksonville, Florida.
authors.forename: David
authors.initials: D
authors.lastname: Wright
authors.affiliation: Tennessee Oncology, Chattanooga, Tennessee.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Anz
authors.affiliation: Center for Cancer and Blood Disorders, Bethesda, Maryland.
authors.forename: Ralph
authors.initials: R
authors.lastname: Boccia
authors.affiliation: H. Lee Moffitt Cancer Center, Tampa, Florida.
authors.forename: Rami S
authors.initials: RS
authors.lastname: Komrokji
authors.affiliation: Department of Internal Medicine, Division of Hematology Oncology, Henry Ford Hospital, Detroit, Michigan.
authors.forename: Philip
authors.initials: P
authors.lastname: Kuriakose
authors.affiliation: Florida Cancer Specialists-South, Cape Coral, Florida.
authors.forename: James
authors.initials: J
authors.lastname: Reeves
authors.affiliation: Leukemia Program, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Mikkael A
authors.initials: MA
authors.lastname: Sekeres
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.affiliation: MEI Pharma, San Diego, California.
authors.forename: Richard
authors.initials: R
authors.lastname: Ghalie
authors.affiliation: Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical.
authors.forename: Gail J
authors.initials: GJ
authors.lastname: Roboz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001374:Azacitidine / Q000008:administration & dosage; D001562:Benzimidazoles / Q000008:administration & dosage; D015415:Biomarkers; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D001562:Benzimidazoles; D015415:Biomarkers; C557525:SB939 compound; D001374:Azacitidine
keywords: azacitidine combinations; clinical trial; histone deacetylase; myelodysplastic syndromes