{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T07:05:52Z","timestamp":1783667152760,"version":"3.55.0"},"reference-count":16,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"<jats:sec id=\"ab-zoi241564-4\"><jats:title>Importance<\/jats:title><jats:p>Three similar phase 3 randomized clinical trials have investigated PD-1\/PD-L1 (programmed cell death 1 protein\/programmed cell death 1 ligand 1) inhibitors in combination with platinum-based chemotherapy vs chemotherapy alone as first-line treatment for advanced urothelial carcinoma (IMvigor130, atezolizumab; KEYNOTE-361, pembrolizumab; and CheckMate901, nivolumab). Only CheckMate901 reported overall survival (OS) benefit for the combination. The reason for these inconsistent results is unclear.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi241564-5\"><jats:title>Objective<\/jats:title><jats:p>To explore whether differential censoring\u2014that is, censoring imbalance between the study groups\u2014is a possible explanation for these inconsistent findings.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi241564-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This comparative effectiveness study involved a censoring analysis of data from IMvigor130, KEYNOTE-361, and CheckMate901, which enrolled patients between 2016 and 2022. Participants included patients in these 3 trials.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi241564-7\"><jats:title>Exposure<\/jats:title><jats:p>Participation in 1 of the 3 trials.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi241564-8\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>The primary outcomes were censoring rates adjusted for treatment effects. Censoring rates were calculated from the Kaplan-Meier (KM) curves. When excess censoring in the control group of open-label trials was found, the hypothesis was that better-performing patients might be dropping out to seek alternative treatments; a sensitivity analysis was conducted in which their survival was assumed to be similar to that of the longest surviving patients in the control group. Treatment effects of the censoring-adjusted KM curves were calculated using the 2-sided log-rank test.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi241564-9\"><jats:title>Results<\/jats:title><jats:p>The 3 trials involved a total of 2162 patients (1640 male [76%]; age range, 65-69 years) Analysis of progression-free survival (PFS) curves demonstrated no differential censoring in IMvigor130, but there was more than 30% excess censoring in the chemotherapy-only groups in KEYNOTE-361 and CheckMate901 trials. After sensitivity analysis, the PFS benefit was no longer significant in either study (KEYNOTE-361, adjusted hazard ratio [HR], 1.13 [95% CI, 0.95-1.35]; CheckMate901, adjusted HR, 1.17 [0.96-1.44]). Analysis of OS curves demonstrated no differential censoring in IMvigor130 or KEYNOTE-361, but there was more censoring in the chemotherapy-only group in CheckMate901. After sensitivity analysis, the OS benefit of adding nivolumab to chemotherapy was lost (before adjustment, HR, 0.77 [95% CI, 0.63-0.95]; <jats:italic>P<\/jats:italic>\u2009=\u2009.01; adjusted HR, 0.95 [95% CI, 0.77-1.17]; <jats:italic>P<\/jats:italic>\u2009=\u2009.64).<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi241564-10\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>In this comparative effectiveness study, differential censoring explained the inconsistent results reported in the evaluated trials. The term <jats:italic>perceived-inferiority censoring<\/jats:italic> is suggested to describe a phenomenon wherein better-performing patients are aware of their treatment and drop out to pursue alternative therapeutic options; it is possible that this occurred in the open-label KEYNOTE-361 and CheckMate901 trials. Such censoring confounds randomization and interpretation of clinical trials, since a larger experimental group is compared with a selected group of controls with poorer prognosis.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2024.55630","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T16:33:24Z","timestamp":1737563604000},"page":"e2455630","source":"Crossref","is-referenced-by-count":7,"title":["Reanalysis of Urothelial Cancer Chemoimmunotherapy Trials With Differential Censoring"],"prefix":"10.1001","volume":"8","author":[{"given":"Tomer","family":"Meirson","sequence":"first","affiliation":[{"name":"Davidoff Cancer Center, Rabin Medical Center, Petach Tikvah, Israel"},{"name":"Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"},{"name":"Samueli Integrative Cancer Pioneering Institute, Rabin Medical Center-Beilinson Hospital, Petach Tikva, 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