The impact of post-progression censoring in second-line immunotherapy studies for mesotheliomaThe impact of post-progression censoring in second-line immunotherapy studies for mesothelioma

Immune checkpoint inhibitors have shown inconsistent benefit in second-line malignant pleural mesothelioma. Because informative censoring may bias time-to-event analyses, we re-evaluated key second-line trials to determine whether censoring patterns contributed to discordant efficacy results. Published Kaplan–Meier (KM) curves from CONFIRM (nivolumab vs placebo), the CONFIRM update, and PROMISE-Meso (pembrolizumab vs chemotherapy) were reconstructed. Censoring distributions were quantified using reverse-KM, and differential censoring between arms and across endpoints (overall survival [OS] vs progression-free survival [PFS]) was evaluated over time. Sensitivity analyses were applied to address excessive censoring, and hazard ratios and restricted mean survival time differences were calculated. In CONFIRM, the initially reported OS advantage coincided with short follow-up and a differential censoring pattern consistent with post-progression censoring. The updated CONFIRM dataset, with longer follow-up, demonstrated no OS benefit and no evidence of post-progression censoring. In contrast, PROMISE-Meso showed no evidence of post-progression censoring at any time and remained negative throughout. When general differential censoring was addressed using sensitivity analyses, both the PFS effect and the OS advantage in CONFIRM lost statistical significance. Post-progression censoring is an under-recognized source of bias that can generate misleading survival signals and may have contributed to the initial CONFIRM findings that were based on a premature early data lock. Although a modest treatment effect in a biologically defined subgroup cannot be excluded, current evidence remains inconclusive. Future studies should ensure comprehensive ascertainment of survival outcomes and include adequately powered biomarker programs.