A phase III randomized, multicentre, double blind, active controlled trial to compare the efficacy and safety of two different anagrelide formulations in patients with essential thrombocythaemia – the TEAM‐ET 2·0 trial

Abstract

Summary Anagrelide is an established treatment option for essential thrombocythaemia ( ET ). A prolonged release formulation was developed with the aim of reducing dosing frequency and improving tolerability, without diminishing efficacy. This multicentre, randomized, double blind, active‐controlled, non‐inferiority trial investigated the efficacy, safety and tolerability of anagrelide prolonged release (A‐ PR ) over a reference product in high‐risk ET patients, either anagrelide‐naïve or ‐experienced. In a 6 to 12‐week titration period the individual dose for the consecutive 4‐week maintenance period was identified. The primary endpoint was the mean platelet count during the maintenance period (3 consecutive measurements, day 0, 14, 28). Of 112 included patients 106 were randomized. The mean screening platelet counts were 822 × 10 9 /l (95% confidence interval ( CI ) 707–936 × 10 9 /l) and 797 × 10 9 /l (95% CI 708–883 × 10 9 /l) for A‐ PR and the reference product, respectively. Both treatments effectively reduced platelet counts, to mean 281 × 10 9 /l for A‐ PR (95% CI 254–311) and 305 × 10 9 /l (95% CI 276–337) for the reference product ( P < 0·0001, for non‐inferiority). Safety and tolerability were comparable between both drugs. The novel prolonged‐release formulation was equally effective and well tolerated compared to the reference product. A‐ PR provides a more convenient dosing schedule and will offer an alternative to licensed immediate‐release anagrelide formulations.

Current management strategies for polycythemia vera and essential thrombocythemia

“…Finally, in the randomized, double-blind active controlled, TEAM-ET trial, a anagrelide prolonged-release formulation was compared to reference product in 106 patients; the study showed non-inferiority of new formulation over the reference in reducing platelet count. Unfortunately, vascular events were not an endpoint of the study [98]. Combination of hydroxyurea and anagrelide in patients whose platelet counts was poorly controlled with monotherapy were shown safe and effective in an observational study in 347 patients [99].…”

Current Concepts of Pathogenesis and Treatment of Philadelphia Chromosome-Negative Myeloproliferative Neoplasms

“…Recently, an extended release formulation of anagrelide was developed that could offer a more convenient dosing schedule. 53 Ruxolitinib has been tested in ET intolerant or resistant to HU, but so far has not proven beneficial. 54,55 The ongoing RUXO-BEAT trial evaluates the role of ruxolitinib as first-line therapy in high-risk PV and ET, and results are awaited.…”