Censoring in trials testing immunotherapy in advanced cancers. A systematic review and a meta-research study

Abstract

Background: Informative censoring affects interpretation of trials results. We investigated censoring rates in randomized controlled trials (RCTs) of immune checkpoint inhibitors (ICIs).

Methods: We searched articles of RCTs testing ICIs in advanced cancers, published up to 12/2023. For both progression free (PFS) and overall survival (OS) Kaplan-Meier (K-M) curves, we collected the rates of censored patients at the first (T1), median PFS/OS (TmPFS/OS) and last (T2) study intervals. We calculated the unweighted difference in censoring rates (ΔC-E) and the weighted difference adjusted for enrolment size (wΔC-E), in control (C) versus experimental (E) arm at T1. Tm and T2.

Results: Of the selected 140 trials, censoring data at T1, Tm and T2 were available for 53/140 (37.8%) and 55/140 (39.2%) trials for PFS and OS K-M curves, respectively. Rates of censoring in C and E were: at T1, 8.19% and 4.92%, for PFS; TmPFS, 15.5% and 12.5%; T1, 2.33% and 1.16%, for OS; TmOS, 20.1% and 21.3%; T2, 23.29% and 26.34%, for PFS; T2, 33.3% and 39.49%, for OS. Analysis of wΔC-E revealed more censoring in C at T1 (PFS: 1.32; OS: 0.40) and in E at T2 (PFS: -2.61; OS: -5.23). Finally, at T1, we found larger rates of censoring in C of open-label compared to double-blinded RCTs.

Conclusions: Multiple RCTs of ICIs did not report censoring data. The rate of censoring is higher in C at the start and increases in E over the course of the trial. Further studies might elucidate the role of censoring on survival outcomes.

Keywords: Immunotherapy; RCTs; advanced cancer; immune checkpoint inhibitors; informative censoring.