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Rebecca Olin, MD, MS


Two Clinical Trial Endpoints May Allow for Earlier Evaluation of Novel AML Therapies

By: Julia Fiederlein
Posted: Tuesday, February 15, 2022

More effective therapies are needed to increase cure rates, extend survival, prevent relapse, and improve quality of life in patients with acute myeloid leukemia (AML). Thus, Richard Pazdur, MD, of the U.S. Food and Drug Administration (FDA) and colleagues conducted a trial to examine the association between response rates, a harmonized definition of event-free survival, and overall survival in newly diagnosed patients who were treated with intensive induction chemotherapy. The results of this analysis were published in the Journal of Clinical Oncology.  

“Use of [the] complete remission rate and event-free survival as clinical trial endpoints could allow earlier evaluation of novel therapies for patients with newly diagnosed AML and may correlate with overall survival,” the investigators remarked. “Thus, both endpoints would be important to study in trials of novel therapeutics in patients with newly diagnosed AML.”

Using trial-level and patient-level data from eight randomized, active-controlled trials of intensive chemotherapy submitted to the FDA, the investigators identified a total of 4,482 patients with newly diagnosed AML. Trial-level analyses revealed a moderate association between odds ratios for the complete remission rate and hazard ratios for overall survival (R2 = 0.49). When event-free survival definitions were harmonized across trials using raw data, a strong association between hazard ratios for event-free survival and overall survival was reported (R2 = 0.87). Based on the results of the patient-level responder analyses, patients who achieved complete remission tended to experience better overall survival outcomes than those who achieved complete remission without full blood cell count recovery (hazard ratio = 0.73) and nonresponders (hazard ratio = 0.33).

In an accompanying Editorial published in the Journal of Clinical Oncology, Courtney D. DiNardo, MD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues commented: “An overall survival endpoint no longer solely reflects the effectiveness of an initial therapy, as survival will also be affected by subsequent lines of AML-directed treatment. The central finding of the article, that both event-free survival and the complete remission rate are reliably associated with improved overall survival, is of immediate relevance and indicates that these parameters represent acceptable and appropriate surrogate endpoints for clinical trials of AML.”

Disclosure: For full disclosures of the study authors, visit

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