ArticleCancer immunology, immunotherapy : CII2026
Real-world effectiveness of avelumab, pembrolizumab, and enfortumab vedotin in patients with advanced urothelial carcinoma with squamous differentiation (ARON-2EV).
Article in Cancer immunology, immunotherapy : CII, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05290038 (ARON-2 Study-Multicentric International Retrospective Study), which is not on this map. Cited by 2 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
ARON-2 Study-Multicentric International Retrospective Study
Who cites it
2 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Immunotherapy in urological cancers: new paradigms and a systematic review of clinical trials and real-world evidence.Frontiers in oncology · 2026Pooled it
- A locally deployed large language model for pathology-informed and nurse-reviewed communication support in bladder cancer immunotherapy.Frontiers in medicine · 2026Article
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31 authors.
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No grant is acknowledged in the PubMed record.
Abstract
introductionAvelumab, pembrolizumab, and enfortumab vedotin (EV) demonstrated efficacy in mUC following platinum-based chemotherapy. However, real-world data in patients with urothelial carcinoma with squamous differentiation (UCSD) are limited. The aim of this study is to assess the real-world clinical outcomes of avelumab, pembrolizumab, or EV in mUCSD patients. MATERIALS AND
methodsThe ARON-2EV study is a retrospective, international, multicenter analysis in patients with mUC treated with avelumab, pembrolizumab, or EV across 79 centers in 21 countries. Patients were divided into three cohorts: 1 (avelumab), 2 (pembrolizumab), and 3 (EV). Primary endpoints were overall survival (OS) and time on treatment (ToT). Secondary objectives included evaluating clinical factors associated with outcomes and exploring the impact of UCSD histology on response to therapy. Statistical methods included Kaplan-Meier estimates, log-rank tests, Fisher's exact and chi-square tests, and Pearson's correlation coefficients.
resultsA total of 1918 patients, 1696 with advanced pure UC (pUC) and 222 with mUCSD (36 in cohort 1, 111 in cohort 2, and 75 in cohort 3), were included. Median OS was shorter in patients with UCSD compared to patients with pUC histology in the three cohorts (1: 13.0 vs 26.8 months, HR 2.66, p = 0.003; 2: 10.2 vs 18.5 months, HR 1.52, p = 0.008; and 3: 7.6 vs 13.1 months, HR 1.68, p = 0.011). Median ToT was shorter in patients with UCSD compared to patients with pUC histology in cohort 1 (3.5 vs 5.6 months, HR 1.57, p = 0.044) and 3 (7.6 vs 13.6 months, HR 1.83, p = 0.005) but not in cohort 2 (3.7 vs 4.7 months, HR 1.19, p = 0.177). Response to therapy was negatively correlated with UCSD histology in cohorts 2 (correlation coefficient 0.094, p = 0.008) and 3 (correlation coefficient 0.107, p = 0.021), while response to avelumab was not correlated with UCSD (correlation coefficient 0.072, p = 0.263).
conclusionsUCSD is a histology with a poor prognosis and response to treatments compared to pUC. Treatments activity and effectiveness in divergent differentiations should be addressed in dedicated prospective studies. TRIAL REGISTRATION NUMBER: NCT05290038.
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