Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2022
Putative Biomarkers of Clinical Benefit With Pembrolizumab in Advanced Urothelial Cancer: Results from the KEYNOTE-045 and KEYNOTE-052 Landmark Trials.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 42 papers, 2 of them syntheses that pooled it.
What it found
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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.
A Phase III Randomized Clinical Trial of Pembrolizumab (MK-3475) Versus Paclitaxel, Docetaxel or Vinflunine in Subjects With Recurrent or Progressive Metastatic Urothelial Cancer
A Phase II Clinical Trial of Pembrolizumab (MK-3475) in Subjects With Advanced/Unresectable or Metastatic Urothelial Cancer
Who cites it
42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 47 citations in OpenAlex.
- Role of tumor mutational burden in patients with urothelial carcinoma treated with immune checkpoint inhibitors: a systematic review and meta-analysis.Frontiers in immunology · 2025Pooled it
- Fibroblast growth factor receptor 3 mutation attenuates response to immune checkpoint blockade in metastatic urothelial carcinoma by driving immunosuppressive microenvironment.Journal for immunotherapy of cancer · 2023Pooled it
- Pembrolizumab plus axitinib versus sunitinib for advanced clear cell renal cell carcinoma: 5-year survival and biomarker analyses of the phase 3 KEYNOTE-426 trial.Nature medicine · 2025Trial
- Association of Tumor Mutational Burden and PD-L1 with the Efficacy of Pembrolizumab with or without Chemotherapy versus Chemotherapy in Advanced Urothelial Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- Association between gene expression signatures and clinical outcomes of pembrolizumab versus paclitaxel in advanced gastric cancer: exploratory analysis from the randomized, controlled, phase III KEYNOTE-061 trial.Journal for immunotherapy of cancer · 2023Trial
- Integrated transcriptome analysis and machine learning to construct a homeostatic model of acetylation for bladder cancer and validate the key geneTranslational andrology and urology · 2026Article
- Review
- OncogenicJournal for immunotherapy of cancer · 2026Article
- Review
- Research progress in augmentation strategies for PD-1/PD-L1 inhibitors in bladder cancer: from biological determinants to clinical applications.Frontiers in immunology · 2026Review
- Tumor-intrinsic execution of interferon-γ-associated immunity in bladder cancer: checkpoints in signaling, recruitment, and recognition.Frontiers in immunology · 2026Review
- BCG Induces PD-1 Upregulation on Circulating CD8Oncology research · 2026Article
- Prognostic and predictive factors of immune checkpoint inhibitor therapy in urinary bladder cancer.Pathology oncology research : POR · 2026Review
- Combining molecular patterns and clinical data for better immune checkpoint inhibitor prediction in metastatic urothelial carcinoma.Cancer immunology, immunotherapy : CII · 2025Article
- Toxicity Profile of New Therapies in Metastatic Urothelial Carcinoma and Its Impact on Treatment Selection.Cancers · 2025Review
- Extracellular vesicles-derived LncRNA MAFG-AS1 predicts clinical response to pembrolizumab in patients with advanced urothelial carcinoma.Molecular biology reports · 2025Article
- Molecular and immune characteristics of neuroendocrine bladder carcinoma - Implications for diagnosis, prognosis, and therapy: A review.Biomolecules & biomedicine · 2025Review
- Association of potential biomarkers with clinical outcomes in metastatic triple-negative breast cancer treated with pembrolizumab or chemotherapy.NPJ breast cancer · 2025Article
- Enfortumab vedotin promotes PD-L1 expression in urothelial carcinoma via NF-κB and STAT3 pathways highlighting mechanisms of immune evasion and potential for combination therapy.BMC immunology · 2025Article
- Article
Corrections and comments
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Authors and funding
31 authors at 20 institutions in 10 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeIn an exploratory analysis, we investigated the association between programmed death ligand 1 (PD-L1), tumor mutational burden (TMB), T-cell-inflamed gene expression profile (TcellinfGEP), and stromal signature with outcomes of pembrolizumab in urothelial carcinoma (UC). PATIENTS AND
methodsPatients with advanced UC received first-line pembrolizumab 200 mg every 3 weeks in the single-arm phase II KEYNOTE-052 trial (NCT02335424) and salvage pembrolizumab 200 mg every 3 weeks or chemotherapy (paclitaxel/docetaxel/vinflunine) in the randomized phase III KEYNOTE-045 trial (NCT02256436). The association of each biomarker (continuous variable) with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) was evaluated using logistic regression (ORR) and Cox PH (PFS, OS), adjusted for ECOG PS; nominal P values were calculated without multiplicity adjustment (one-sided, pembrolizumab; two-sided, chemotherapy). Significance was prespecified at α = 0.05.
resultsIn KEYNOTE-052, PD-L1, TMB, and TcellinfGEP were significantly associated with improved outcomes; stromal signature was significantly associated with worse outcomes. In KEYNOTE-045, although findings for TMB and TcellinfGEP with pembrolizumab were consistent with those of KEYNOTE-052, PD-L1 was not significantly associated with improved outcomes, nor was stromal signature associated with worse outcomes with pembrolizumab; chemotherapy was not associated with outcomes in a consistent manner for any of the biomarkers. Hazard ratio (HR) estimates at prespecified cutoffs showed an advantage for pembrolizumab versus chemotherapy regardless of PD-L1 or TMB, with a trend toward lower HRs in the combined positive score ≥10 and the TMB ≥175 mutation/exome subgroup. For TcellinfGEP, PFS and OS HRs were lower in the TcellinfGEP-nonlow subgroup regardless of treatment.
conclusionsMultiple biomarkers characterizing the tumor microenvironment may help predict response to pembrolizumab monotherapy in UC, and potential clinical utility of these biomarkers may be context-dependent.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.