OA: Basket Trials in Oncology: A Trade-Off Between Complexity and Efficiency

Basket Trials in Oncology: A Trade-Off Between Complexity and Efficiency

The current oncology drug development landscape is dominated by efforts to create therapies that are mechanistically designed to improve outcomes for patients with cancers that harbor specific molecular aberrations, which often occur across a variety of tumor types. In the evaluation of targeted therapies, basket trials have emerged as an approach to test the hypothesis that targeted therapies may be effective independent of tumor histology, as long as the molecular target is present.¹ However, the term basket has been applied broadly, and there is little uniformity in the design or goals of these trials. Furthermore, the scientific goals frequently are not specified with the precision conventionally used for clinical trials, leading to some difficulties in design and interpretation. For instance, many investigative teams use the popular Simon two-stage design, independently in each basket, thus effectively treating the trial overall as a series of independent phase II clinical trials. However, the actual goals are typically more complex than those of simple phase II clinical trials of new agents. In this commentary, we present an overview of the various trials described as basket trials, clarify the distinctive goals that basket trials seek to address, discuss the inherent hidden complexities, and offer general recommendations regarding their design.....