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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.
Kantarjian, Hagop M. MD, PhD 1; Martinelli, Giovanni MD, PhD 2; Jabbour, Elias J. MD 1; Quintas-Cardama, Alfonso MD 1; Ando, Kiyoshi MD, PhD 3; Bay, Jacques-Olivier MD, PhD 4; Wei, Andrew PhD 5; Gropper, Stefanie MD 6; Papayannidis, Cristina MD 2; Owen, Kate MD, FFPM 7; Pike, Laura MSc 7; Schmitt, Nicola MPhil 7; Stockman, Paul K. MBChB, PhD 7; Giagounidis, Aristoteles MD, PhD 6; SPARK-AML1 Investigators
[Article] Cancer. 119(14):2611-2619, July 15, 2013.

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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. Cancer 2013;119:2611-2619. (C) 2013 American Cancer Society.

A significant improvement in the objective complete response rate is observed with 1200 mg barasertib versus 400 mg low-dose cytosine arabinoside in older patients with acute myeloid leukemia. The safety profile of barasertib, although more toxic than that of low-dose cytosine arabinoside, is manageable and consistent with previous studies.