Chapter 3 52 therapies in AML. Therefore, we evaluated targeted drug development during twenty years of clinical research in AML based on progression of distinct drugs from phase II to phase III to FDAapproval. Additionally, we assessed the benefits through the Magnitude of Clinical Benefit Scale (MCBS) of the European Society for Medical Oncology (ESMO).9 Through a combination of study type (randomized or not), setting (curative or non-curative), endpoints (quality of life, survival, response rates), and statistical significance, the ESMO-MCBS v1.1 is developed specifically to evaluate the clinical benefit of oncology drugs, and has been successfully adopted in the assessment of hematological drugs. A detailed explanation of this scale can be found in the work of Kiesewetter and colleagues.10 We searched for trials in AML in ClinicalTrials.gov, and categorized all studies based on drug, target, and clinical end points. We found that between January 2000 and September 2020, 167 distinct pharmaceutical agents with 96 targets were investigated in 397 phase II trials (Figure 1). All phase II results Exclude Chemo-only trials Endocrine trials Biomarker trials Vaccine-based T-Cell based HSCT / GvHD CML, ALL, APL All phase III results N = 1328 MEDLINE through PubMed ClinicalTrials.gov All phase III results N = 300 N = 285 N = 397 N = 64 Exclude overlap N = 23 N = 64 Final targeted phase II trials Final targeted phase III trials Figure 1: Search strategy. Phase II and III trials were identified through ClinicalTrials.gov. Additional published phase III trials were identified in MEDLINE through PubMed. Of the phase III trials, we evaluated whether published results were available that were not yet identified in the PubMed search.
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