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Abstract
Background The pomalidomide pivotal clinical trial was recently published in Lancet Oncology (PubMed PMID:24007748). Pomalidomide shows a significant benefit on overall survival (OS), with a difference between medians of 4.6 months (12.7 vs. 8.1). However, difference in median survival (DMS) is erratic and sometimes doesn’t provide a good assessment of survival benefit.
Purpose To reanalyse pomalidomide OS benefit from pivotal clinical trial using an area under the curve (AUC)-based method.
Materials and methods Kaplan-Meier OS curves were extracted from the pomalidomide pivotal clinical trial. A graphical AUC method was applied to pomalidomide + low-dose dexamethasone vs. high-dose dexamethasone curves and compared to DMS.
– Using the AUC method, three lines were defined for pomalidomide OS graph: V, H and T. A vertical cutting line (V) intersects the abscissa at the longest time (t) with at least 10 patients at risk in each group or 30 in total. A horizontal cutting line (H) intersects the point where V and the upper curve cross. AUC was defined between the ordinate axis, the curve and H. A reference area (RA) was defined as the rectangular area between the ordinate axis, V, H and T. It represents the survival time in the event that no patients died (t). The AUC method quantifies the difference between areas, relates them to a RA and the results are expressed in units of time.
– Survival reanalysis was calculated as (AUC/RA)*t for each curve. Photoshop CS6 was used for graphical AUC calculation.
Results The V-line intersects the abscissa with 31 patients at risk for a “t” equal to 16 months. With 61.5% patients included in this AUC-based analysis (the H line), pomalidomide + low-dose dexamethasone AUC was 91602 pixels, high-dose dexamethasone AUC, 59240 pixels and RA, 196968 pixels. OS reanalysis and comparison to DMS are shown in the table below.
Conclusions The pomalidomide OS AUC-based method gives a value 2 months less than DMS and could have relevant implications for pomalidomide evaluation, positioning and cost utility in clinical practice.
No conflict of interest.