455P - Evolution of Clinical Trial Design in Early Drug Development: The Use of Expansion Cohorts (ECS) in Phase I Cancer Trials (PITS)

Abstract

ABSTRACT Background ECs are frequently used to optimize the yield of PITs. However, their rationale and value have yet to be evaluated. Here, we explore the prevalence, characteristics and objectives of ECs in single-agent PITs. Methods We conducted a systematic review using MEDLINE and EMBASE to identify all adult single-agent PITs published after 2006. Eligibility assessment and data extraction were performed by 2 reviewers. The primary endpoint was the proportion of PITs with ≥ 1 EC. Additional endpoints included factors associated with EC inclusion and whether the EC objectives were stated and achieved. Results 4,557 articles were reviewed and 591 trials met eligibility criteria. 139 (24%) included ≥ 1 EC. Use of ECs in single-agent PITs increased between 2006 and 2011 (12.2% to 35.7%, Spearman's rho 0.20, p Conclusions The utilization of ECs in PITs has increased with time and is more common for multi-center trials of non-cytotoxic agents. Safety and efficacy are common objectives but 26% failed to report explicit aims. Although the majority of ECs supplement PITs with meaningful safety data, their role in assessing preliminary efficacy requires better definition. Disclosure All authors have declared no conflicts of interest.