Duration of disease control (DDC) or time to failure of strategy (TFS) to evaluate a chemotherapy strategy in advanced colorectal cancer (ACC)

Abstract

4073 Background: Progression-free survival (PFS) is not an optimal endpoint in therapeutic strategies evaluating either stop and go or alternated therapies, or a fixed sequence of two therapies. DDC (Tournigand, JCO 2006) and TFS (Allegra, JCO 2007) composite endpoints have been proposed to evaluate efficacy of these strategies in ACC. This study compared these two alternative endpoints. Methods: DDC is defined as the sum of the PFS of each sequence, except when progressive disease is observed at either reintroduction or second-therapy (DDC=PFS1+PFS2 if treatment 2 achieved stabilization or response). TFS is defined as the total PFS from the initiation of the strategy to disease progression while on all the planned agents, or disease progression during a treatment-free interval and no further therapy received within 1 month, or death (TFS=PFS 1+2). Both DDC and TFS have been calculated in three trials: OPTIMOX1 (oxaliplatin stop and go vs continuous administration, updated database, Tournigand, JCO 2006), OPTIMOX2 (oxaliplatin stop and go vs complete stop and go, updated database, Maindrault-Goebel, ASCO 2007) and C97–3 (FOLFIRI1- FOLFOX6 or reverse sequence, Tournigand 2004). Results: The median potential follow-up time was 39.8 months. There was a moderately shorter DDC than TFS in the two stop and go studies, but a much shorter DDC than TFS in the sequential therapy study. There was a significant correlation between DDC and OS (r=0.96, p=.002) but not between TFS and OS (r=0.71, p=.11) Conclusions: Two bias impacted TFS 1) the results of resuming the planned therapeutic strategy for progression after a chemotherapy-free interval of more than one month was not considered, 2) patients who were not progressive at the end of planned strategy could not be censored at that time. The shorter duration of DDC over TFS may have an advantage in terms of sample size for evaluation of therapeutic strategies. In case of drug registration, DDC does not increase in case of inactive second sequence. [Table: see text] No significant financial relationships to disclose.