title: Stage I of a phase 2 study assessing the efficacy, safety, and tolerability of barasertib (AZD1152) versus low-dose cytosine arabinoside in elderly patients with acute myeloid leukemia.
abstract: BACKGROUND
  In this phase 2 study, the authors evaluated the efficacy, safety, and tolerability of the Aurora B kinase inhibitor barasertib compared with low-dose cytosine arabinoside (LDAC) in patients aged ≥ 60 years with acute myeloid leukemia (AML).
  
  
  METHODS
  Patients were randomized 2:1 to receive either open-label barasertib 1200 mg (as a 7-day intravenous infusion) or LDAC 20 mg (subcutaneously twice daily for 10 days) in 28-day cycles. The primary endpoint was the objective complete response rate (OCRR) (complete responses [CR] plus confirmed CRs with incomplete recovery of neutrophils or platelets [CRi] according to Cheson criteria [also requiring reconfirmation of CRi ≥21 days after the first appearance and associated with partial recovery of platelets and neutrophils]). Secondary endpoints included overall survival (OS) and safety.
  
  
  RESULTS
  In total, 74 patients (barasertib, n = 48; LDAC, n = 26) completed ≥1 cycle of treatment. A significant improvement in the OCRR was observed with barasertib (35.4% vs 11.5%; difference, 23.9%; 95% confidence interval, 2.7%-39.9%; P < .05). Although the study was not formally sized to compare OS data, the median OS with barasertib was 8.2 months versus 4.5 months with LDAC (hazard ratio, 0.88; 95% confidence interval, 0.49-1.58; P = .663). Stomatitis and febrile neutropenia were the most common adverse events with barasertib versus LDAC (71% vs 15% and 67% vs 19%, respectively).
  
  
  CONCLUSIONS
  Barasertib produced a significant improvement in the OCRR versus LDAC and had a more toxic but manageable safety profile, consistent with previous studies.
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. hkantarjian@mdanderson.org
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Elias J
authors.initials: EJ
authors.lastname: Jabbour
authors.forename: Alfonso
authors.initials: A
authors.lastname: Quintás-Cardama
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ando
authors.forename: Jacques-Olivier
authors.initials: JO
authors.lastname: Bay
authors.forename: Andrew
authors.initials: A
authors.lastname: Wei
authors.forename: Stefanie
authors.initials: S
authors.lastname: Gröpper
authors.forename: Cristina
authors.initials: C
authors.lastname: Papayannidis
authors.forename: Kate
authors.initials: K
authors.lastname: Owen
authors.forename: Laura
authors.initials: L
authors.lastname: Pike
authors.forename: Nicola
authors.initials: N
authors.lastname: Schmitt
authors.forename: Paul K
authors.initials: PK
authors.lastname: Stockman
authors.forename: Aristoteles
authors.initials: A
authors.lastname: Giagounidis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D064107:Aurora Kinase B; D064127:Aurora Kinases; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D009503:Neutropenia / Q000139:chemically induced; D010755:Organophosphates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013280:Stomatitis / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: C520647:2-((3-((4-((5-(2-((3-fluorophenyl)amino)-2-oxoethyl)-1H-pyrazol-3-yl)amino)quinazolin-7-yl)oxy)propyl)(ethyl)amino)ethyl dihydrogen phosphate; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D010755:Organophosphates; D011799:Quinazolines; D003561:Cytarabine; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases
keywords: AZD1152; acute myeloid leukemia; barasertib; low-dose cytosine arabinoside