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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.

AbstractBACKGROUND:
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.
AuthorsHagop M Kantarjian, Giovanni Martinelli, Elias J Jabbour, Alfonso Quintás-Cardama, Kiyoshi Ando, Jacques-Olivier Bay, Andrew Wei, Stefanie Gröpper, Cristina Papayannidis, Kate Owen, Laura Pike, Nicola Schmitt, Paul K Stockman, Aristoteles Giagounidis, SPARK-AML1 Investigators
JournalCancer (Cancer) Vol. 119 Issue 14 Pg. 2611-9 (Jul 15 2013) ISSN: 1097-0142 [Electronic] United States
PMID23605952 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
Copyright© 2013 American Cancer Society.
Chemical References
  • 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
  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Organophosphates
  • Quinazolines
  • Cytarabine
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein Serine-Threonine Kinases
Topics
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic (therapeutic use)
  • Antineoplastic Agents (administration & dosage, adverse effects, therapeutic use)
  • Aurora Kinase B
  • Aurora Kinases
  • Cytarabine (administration & dosage, adverse effects, therapeutic use)
  • Drug Administration Schedule
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid, Acute (drug therapy)
  • Male
  • Neutropenia (chemically induced)
  • Organophosphates (administration & dosage, adverse effects, therapeutic use)
  • Protein Serine-Threonine Kinases (antagonists & inhibitors)
  • Quinazolines (administration & dosage, adverse effects, therapeutic use)
  • Stomatitis (chemically induced)
  • Treatment Outcome

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