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Association of Response Rate and Event-Free Survival With Overall Survival in Newly Diagnosed AML: FDA Analysis


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In a trial-level analysis of randomized studies submitted to the U.S. Food and Drug Administration (FDA) reported in the Journal of Clinical Oncology, Norsworthy et al found that complete remission rate was moderately correlated, and event-free survival was strongly correlated, with overall survival in patients receiving intensive chemotherapy for newly diagnosed acute myeloid leukemia (AML). 

Study Details

The analysis included data from eight randomized trials with a total of 4,482 patients submitted between 2007 and 2017. Trial-level odds ratios for complete remission and complete remission plus complete remission with incomplete hematologic or platelet recovery and hazard ratios for event-free survival and overall survival were analyzed using weighted linear regression models. A patient-level analysis evaluated the association of complete remission and complete remission with incomplete hematologic or platelet recovery with overall survival in the pooled population from all trials.

Key Findings

In trial-level analysis, moderate associations were observed between the hazard ratio for overall survival and odds ratios for complete remission (R2 = 0.49, 95% confidence interval [CI] = 0.05–0.86) and for complete remission plus complete remission with incomplete hematologic or platelet recovery (R2 = 0.48, 95% CI = 0.05–0.99).

In trial-level analysis using individual trial protocol definitions of event-free survival, the association between the hazard ratio for overall survival and the hazard ratio for event-free survival was moderate (R2 = 0.60, 95% CI = 0.03–0.97). An analysis was performed using raw data in a harmonized definition of event-free survival as time to treatment failure (including complete remission with incomplete hematologic or platelet recovery), relapse from complete remission, or death from any cause. On the basis of the harmonized definition, a strong association was observed (R2 = 0.87, 95% CI = 0.47–0.98).

In the patient-level analysis, overall survival was improved in patients with complete remission vs those with complete remission with incomplete hematologic or platelet recovery (hazard ratio [HR] = 0.73, 95% CI = 0.64–0.84) and vs nonresponders (HR= 0.33, 95% CI = 0.31–0.37).

The investigators concluded, “On a trial level, there is a moderate association between overall survival and complete remission rate. A strong association between event-free survival and overall survival was observed. However, confidence intervals were wide, and results became moderate using alternative definitions for event-free survival. Patient-level analyses showed complete remission responders have better overall survival compared with complete remission with incomplete hematologic or platelet recovery responders and nonresponders. A therapy in newly diagnosed AML with benefit in event-free survival or substantial benefit in complete remission rate would be likely to have an overall survival effect.”

Kelly J. Norsworthy, MD, of the Center for Drug Evaluation and Research, U.S. Food and Drug Administration, is the corresponding author for the Journal of Clinical Oncology article. 

Disclosure: For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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