Volasertib plus low-dose cytarabine increased the response rate and improved survival in AML patients ineligible for intensive treatment.
Volasertib plus low-dose cytarabine resulted in responses across all AML genetic subgroups and had a clinically manageable safety profile.
Treatment outcomes for older patients with acute myeloid leukemia (AML) have remained dismal. This randomized, phase 2 trial in AML patients not considered suitable for intensive induction therapy compared low-dose cytarabine (LDAC) with or without volasertib, a highly potent and selective inhibitor of polo-like kinases. Eighty-seven patients (median age 75 years) received LDAC 20 mg b.i.d. subcutaneously days 1-10 or LDAC + volasertib 350 mg intravenously days 1 + 15, every 4 weeks. Response rate (complete remission [CR] and CR with incomplete blood count recovery [CRi]) was higher for LDAC + volasertib versus LDAC (31.0% vs 13.3%; odds ratio, 2.91; P=.052). Responses in the LDAC + volasertib arm were observed across all genetic groups, including 5 of 14 patients with adverse cytogenetics. Median event-free survival was significantly prolonged by LDAC + volasertib compared with LDAC (5.6 vs 2.3 months; hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.35-0.92; P=.021); median overall survival was 8.0 versus 5.2 months, respectively (HR, 0.63; 95% CI, 0.40-1.00; P=.047). LDAC + volasertib led to an increased frequency of adverse events that was most pronounced for neutropenic fever/infections and gastrointestinal events; there was no increase in the death rate at days 60 + 90. This study was registered at ClinicalTrials.gov, identifier: NCT00804856.
- Submitted March 7, 2014.
- Accepted June 18, 2014.
- Copyright © 2014 American Society of Hematology