Volasertib for the treatment of acute myeloid leukemia: a review of preclinical and clinical development.

Volasertib is a potent inhibitor of Polo-like kinase (PLK) 1 and to lesser extent also PLK2 and PLK3. PLKs are key regulators of the cell cycle and volasertib blocks cells in G2-M phase of the cell cycle. The compound has been evaluated in Phase I and II studies in acute myeloid leukemia and solid tumors. Side effects are mainly hematological. In acute myeloid leukemia (AML), a randomized Phase II study has been conducted in elderly patients unfit for intensive chemotherapy. Patients have been randomized to a combination of volarsetib and low-dose cytarabine versus low-dose cytarabine alone. Preliminary results show significantly higher rates of complete remission and of complete remission with incomplete hematological recovery in the combination versus the monotherapy arm, with 31% and 13%, respectively. Longer event-free survival was observed with the combination with 5.6 versus 2.3 months, respectively (p = 0.0237). These encouraging data supported the initiation of an international Phase III trial, which currently underway, to confirm these results. Volasertib has not yet been approved for regular clinical use.

RCT Entities:   Population Interventions Outcomes