Two decades of targeted therapies in acute myeloid leukemia

• Published in: Leukemia Vol. 35; no. 3; pp. 651 - 660
• Main Authors: Cucchi, David G. J., Polak, Tobias B., Ossenkoppele, Gert J., Uyl–De Groot, Carin A., Cloos, Jacqueline, Zweegman, Sonja, Janssen, Jeroen J. W. M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2021; Nature Publishing Group
• Subjects: 631/67/1990/283/1897; 692/308/153; 692/308/2779/109/1941; 692/308/2779/109/1942; Acute myeloid leukemia; Antineoplastic Agents - therapeutic use; Cancer Research; Clinical trials; Critical Care Medicine; Drug development; Drugs; Hematology; Humans; Intensive; Internal Medicine; Leukemia; Leukemia, Myeloid, Acute - drug therapy; Medicine; Medicine & Public Health; Methods; Molecular Targeted Therapy; Myeloid leukemia; Oncology; Patients; Precision Medicine; Quality of Life; Review Article; Netherlands
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/s41375-021-01164-x

Precision medicine is gaining importance in the treatment of acute myeloid leukemia (AML). Objectively reviewing past and current knowledge aids guiding future research. Therefore, we provide a complete overview of all phase II and phase III trials investigating targeted therapies in AML and their primary endpoints over the past two decades in perspective of their clinical benefit. We assessed whether drugs were primarily designed to treat AML or were repurposed and how successful they were based on progression of distinct drugs from phase II to phase III to FDA-approval. Between January 2000 and September 2020, 167 agents with 96 targets were investigated in 397 phase II trials. Twenty-eight agents were steered towards phase III, after three phase II trials on average. Repurposed drugs less often advanced in clinical development than drugs primarily developed for AML. Composite responses were the most prevalent primary endpoints in phase II. Of the eight FDA-approved drugs, none investigated quality of life at time of approval, and three out of eight have yet to show benefit in overall survival. Returns on targeted therapy research remain lean for AML patients. Future trials should not overlook non-targeted agents and foremost study endpoints proven to predict patient well-being.