Acute myeloid leukaemia ( AML ) is an aggressive and devastating blood cancer. It predominantly affects people over 60 and is one of the most common adult leukaemias in the Western World. The current standard of care is intensive chemotherapy, but many older patients cannot tolerate this therapeutic approach; their options are limited and their prognosis is poor.
For older AML patients not suitable for intensive chemotherapy, low dose Cytarabine ( LDAC ) is a well-established form of chemotherapy.
Volasertib has shown in recent studies to be a potentially promising alternative treatment for these patients. In a phase II clinical trial Volasertib, combined with low dose Cytarabine, led to prolonged survival times and more than doubled the percentage of patients achieving remission compared to LDAC alone.
Volasertib was awarded Breakthrough Therapy designation by the U.S. Food and Drug Administration ( FDA ) in 2013 and Orphan Drug Designation by the FDA and the European Commission in 2014.
Volasertib is an investigational, selective and potent inhibitor of enzymes called Polo-like kinases ( Plks ). Plk1, the best understood of the five known Plks, has an important role in cell division. Inhibition of Plk1 by Volasertib results in cell cycle arrest with subsequent induction of apoptosis ( programmed cell death ).
Volasertib is currently being evaluated in clinical trials for acute myeloid leukaemia. The results of the phase II clinical trial published in Blood included the following endpoints:
a) response rate ( complete remission or complete remission with incomplete blood count recovery ) was more than doubled for patients receiving Volasertib and low dose Cytarabine vs LDAC alone ( 31% vs 13.3%, 13 of 42 patients vs 6 of 45 patients; odds ratio, 2.91; P=0.052 );
b) median event-free survival was prolonged in patients receiving Volasertib and low dose Cytarabine vs LDAC alone ( 5.6 months vs. 2.3 months; hazard ratio [ HR ] 0.57, 95% confidence interval [ CI ], 0.35–0.92; P=0.021 );
c) remissions achieved by the combination appeared to be more durable ( the relapse free survival for Volasertib and low dose Cytarabine vs LDAC alone was 18.5 vs. 10.0 months, 13 vs 6 patients );
d) median overall survival was 8.0 months vs 5.2 months, respectively ( HR 0.63, 95% CI, 0.40-1.00; P=0.047 );
e) responses in patients receiving Volasertib and low dose Cytarabine were observed across all genetic groups, including 5 of 14 AML patients with adverse genetics;
f) patients receiving Volasertib and low dose Cytarabine showed a higher rate of adverse effects, in particular febrile neutropenia grade 3 ( 38% vs. 7% ), infections grade 3 ( 38% vs. 7% ) and gastrointestinal adverse reactions grade 3 ( 21% vs. 7% ). ( Xagena )
Source: Boehringer Ingelheim, 2014