Abstract | BACKGROUND: 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.
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Authors | Hagop 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 |
Journal | Cancer
(Cancer)
Vol. 119
Issue 14
Pg. 2611-9
(Jul 15 2013)
ISSN: 1097-0142 [Electronic] United States |
PMID | 23605952
(Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
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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
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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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