PB1719 TRENDS IN EFFICACY PARAMETERS STUDIED IN CLINICAL TRIALS FOR ACUTE MYELOID LEUKAEMIA

Abstract

Background:Acute myeloid leukaemia (AML) accounts for one third of adult leukaemias in developing countries and is associated with poor prognosis in Europe. Biomarker‐based endpoints have been validated as surrogate measures to predict overall survival (OS) in AML, potentially leading to shorter clinical trial (CT) durations and faster patient access to innovative treatments.Aims:To analyse the evolvement of efficacy endpoints over time for CTs in AML conducted in the European Union (EU).Methods:Interventional Phase II to Phase IV AML CTs registered in the EU Clinical Trials Register over an 11‐year period (2007‐2017) were identified. Therapeutic CTs reporting efficacy data in the English language for investigational medicinal products (IMPs) of chemical, biological and biotechnological origin were included in the study. A protocol design or age filter was not applied to avoid limiting the scope of outcomes identified. Primary and secondary efficacy endpoints were extracted from the selected CTs and categorised according to type of measurement. Descriptive and inferential statistics were operated in a data mining process to detect trends in outcomes studied by pharmaceutical developers.Results:The final data set comprised 161 CTs representing 46,914 patients, with the majority of trials (67%, n=108) recruiting only patients from the adult (18‐64 years) and elderly (>=65 years) populations. Twenty‐nine unique efficacy measures were identified and stratified into the endpoint clusters of survival (n=4), time‐to‐event (n=5), response rates and biomarkers (n=13) and other (n=7) parameters. Sixty‐eight per cent (n=110) of the trials reported 4‐10 outcomes, with a mean of 5 per CT. The principal outcomes examined included OS (CTs: 78%, n=126), complete response rate (CR) (CTs: 52%, n=84) and event‐free survival (EFS) (CTs: 44%, n=71). The endpoints EFS, OS and complete response rate with incomplete blood recovery (CRi) registered the highest frequency change of selection pre‐ and post‐2012 (EFS: 30%, p < 0.001; OS: 27%, p < 0.001; CRi: 18%, p = 0.01).Summary/Conclusion:The increase in uptake of EFS and CRi as efficacy parameters in AML CTs is in line with previous findings correlating these measures to OS. Significant heterogeneity in the selection of efficacy endpoints was observed. This warrants future work on the development of a core, standardised set of efficacy outcomes prioritised by relevant stakeholders for AML CTs.