Reporting disease control rates or clinical benefit rates in early clinical trials of anticancer agents: useful endpoint or hype?

Abstract Disease Control Rate (DCR) and Clinical Benefit Rate (CBR) are defined as the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease to a therapeutic intervention in clinical trials of anticancer agents. DCR and CBR are commonly reported in many clinical trials in abstracts, papers, meeting presentations and media releases. The frequent use of these measures of drug activity presents the question of whether DCR and CBR are useful additional endpoints in early clinical trials, and if they can reasonably predict the success of an agent in subsequent, adequately powered, randomized trials. There are no comprehensive analyses to demonstrate that CBR and DCR add to the value of traditional response/activity endpoints in early clinical trials. Data from phase II clinical trials in which the DCR or CBR are reported suggest that DCR or CBR provides ambiguous information that likely exaggerates the anticancer activity of the therapy. The terms 'disease control' and 'clinical benefit' in the context of non-randomized trials are themselves disingenuous because neither tumor regression nor stable disease, defined without any consideration of duration of effect or reduction of symptoms appropriate for the specific patient population, are evidence of these endpoints in an individual patient.