Premature clinical trial discontinuation in all and genitourinary (GU) cancers in the era of immune checkpoint inhibitors (ICI).

Abstract

394 Background: Clinical trial completion is critical for evaluating new therapies. Premature termination or withdrawal of clinical trials is common, impairs progress and results in waste of resources. We assessed features and reasons of early terminated and withdrawn cancer trials focusing on trials with ICI (anti-CTLA-4, anti-PD-1, anti-PD-L1). Methods: We reviewed all adult, intervention, cancer clinical trials registered in ClinicalTrials.gov from November 16, 2011 to April 16, 2015 to identify all early terminated and withdrawn trials. Reasons for termination were captured. Logistics regression model was used to identify factors associated with early termination or withdrawal. Discontinuation rate was compared between ICI and all trials (χ2); p < 0.05 was set as significant. Results: We identified 12875 clinical trials (35% industry-funded, 12% federal-funded; 772 in prostate and 386 in non-prostate GU cancers); 8.5% of all trials were prematurely terminated (5%) or withdrawn (3.5%); main reason for discontinuation was poor accrual (33%) followed by logistical reasons (26%). When comparing trials with ICI (n = 350) to all cancer trials, lower rate of termination or withdrawal was noted with ICI [5.4% vs 8.5%, p = 0.05]. Trials with ICI were less likely to discontinue due to poor accrual compared to all trials, but the difference was not significant (21% vs 33%, p = 0.4). Of the 1158 GU cancers trials, 75 (6.5%) were prematurely terminated and 56 (4.8%) withdrawn; reasons for discontinuation are shown in the table. Conclusions: Poor accrual represents the main cause of early termination of all cancer clinical trials. Premature termination/withdrawal rate appears lower in ICI trials which may be attributed to accrual differences. Clinical trial completion remains a high priority. [Table: see text]