Stage I findings of a two-stage phase II study to assess the efficacy, safety, and tolerability of barasertib (AZD1152) compared with low-dose cytosine arabinoside (LDAC) in elderly patients (pts) with acute myeloid leukemia (AML).

Abstract

6527 Background: Barasertib is the pro-drug to barasertib-hQPA, a selective Aurora B kinase inhibitor with preliminary anti-AML activity in a Phase I/II study (Löwenberg et al. Blood 2011;118:6030). Methods: AML pts aged ≥60 y considered unsuitable for intensive chemotherapy were randomized 2:1 to open-label barasertib 1200 mg (7-day iv infusion) or LDAC 20 mg (sc twice daily for 10 days) in 28-day cycles (NCT00952588). The primary endpoint was improved objective complete response rate (OCRR: CR + CRi [Cheson criteria, but requiring CRi confirmation ≥21 days after first appearance, with partial recovery of platelets and neutrophils]). Secondary endpoints included duration of response (DoR), overall survival (OS) and safety. Results: 74 pts (barasertib, 48; LDAC, 26) received treatment and all completed ≥1 cycle. A significant improvement in OCRR was observed with barasertib (35.4% [17/48] vs 11.5% [3/26]; difference, 23.9% [95% CI, 2.7-39.9]; P<0.05); barasertib responses were seen in all cytogenetic risk groups and appeared to be durable (median DoR [range], 82 [28-321] days; vs LDAC 30-85 days). Although not formally sized to compare OS data, a trend favoring barasertib was observed (HR=0.88, 95% CI, 0.49-1.58; P=0.663; median OS, 8.2 vs 4.5 mo). Stomatitis and febrile neutropenia were the most common adverse events (AEs) in the barasertib arm with higher incidences vs LDAC (71% vs 15%; 67% vs 19%, respectively). Grade ≥3 AEs with a greater incidence in the barasertib arm were febrile neutropenia (50% vs 19%), stomatitis (29% vs 0%) and pneumonia (25% vs 8%); grade ≥3 infection rates were also higher with barasertib (40% vs 23%). For both arms, there were similar discontinuation rates due to AEs (barasertib 8.3% vs LDAC 7.7%), deaths due to AEs (12.5% vs 11.5%) and 30-day mortality (12.5% vs 15.4%). Cumulative toxicities were not observed with barasertib treatment. Conclusions: In this population with poor prognosis using standard chemotherapy, barasertib showed a significant improvement in OCRR vs LDAC, and a safety profile that was manageable and consistent with previous studies.