Bruno Medeiros on How to Interpret AML Clinical Trial Data


In the emerging era of personalized treatment, it may be time to rethink which surrogate markers are used in AML clinical trials.

Molecular advances may allow for a change in how acute myeloid leukemia (AML) patients are evaluated in clinical trials. Currently, overall survival (OS) continues to be the most clinically relevant and preferred endpoint in phase III trials with AML patients. However, in a review article in Leukemia Research, Bruno C. Medeiros, MD, director of the inpatient hematology service at Stanford University School of Medicine, Palo Alto, Calif., stresses that it may be worth discussing the use of other surrogate outcomes, such as event-free survival (EFS), as primary endpoints in future clinical trials.

 According to Medeiros, it might be possible to shorten the clinical development process if EFS were used as a surrogate outcome. Interpretation of individual endpoints must be viewed carefully, Medeiros emphasizes, and clinicians should consider the trial’s statistical design and variations in reporting of endpoints.

He notes that while time-to-event endpoints are typically reported using Kaplan-Meier curves, statistical data derived from these curves can be complex, and a variety of factors may impact interpretation. The purpose of his review article was to take a closer look at the nuances of common AML trial endpoints and their data presentation. He contends that this is vital for understanding and interpreting clinical trial data.

Recently, the treatment regimens for AML have changed. Thanks to new molecular advances, personalized medicine is an emerging option. In turn, new therapeutic options are raising new considerations for clinical trial design, statistical interpretation of outcomes, and methods of reporting data.

Currently, AML clinical trials use five main endpoints to determine the efficacy of new agents: complete response, OS, EFS, relapse-free survival, and disease-free survival. Medeiros contends that understanding how events are defined in a clinical trial, as well as which populations are included and how data are censored, is crucial for evaluating the data effectively.

The US Food and Drug Administration has already approved targeted therapies for AML, including midostaurin (a multitargeted FMS-like tyrosine kinase 3 inhibitor), enasidenib (an isocitrate dehydrogenase 2–targeted inhibitor), CPX-351 (a liposomal daunorubicin/cytarabine combination), and gemtuzumab ozogamicin (a CD33-directed antibody–drug conjugates). Similar agents are completing phase III trials. “Careful interpretation of endpoints used in late-phase AML clinical trials is essential to understanding and evaluating the efficacy of new drugs,” says Medieros.

David J. Prelutsky, MD, an associate professor of clinical medicine at Washington University School of Medicine, St. Louis, agrees that it may be time to rethink which surrogate markers are used in AML clinical trials. “Using event-free survival as a surrogate marker certainly is one way to measure a patient’s quality of life, which may be more important to some patients. Some patients are more interested in quality of life instead of quantity of life, especially when they have advanced disease,” Dr. Prelutsky told Cancer Network.

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