ArticleCancer immunology, immunotherapy : CII2023
Use of concomitant proton pump inhibitors, statins or metformin in patients treated with pembrolizumab for metastatic urothelial carcinoma: data from the ARON-2 retrospective study.
Registry-linked trialOpen access · greenAbstract read
In one paragraph
Article in Cancer immunology, immunotherapy : CII, 2023. 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 22 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 3 pooled it
8.3field-weighted citation impact, top 2% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
22 citing papers in PubMed, 3 syntheses or guidelines pooled it, 26 citations in OpenAlex.
- Pooled it
- The impact of ECOG performance status on efficacy of immunotherapy and immune-based combinations in cancer patients: the MOUSEION-06 study.Clinical and experimental medicine · 2023Pooled it
- The impact of ECOG performance status on efficacy of immunotherapy and immune-based combinations in cancer patients: the MOUSEION-06 study.Clinical and experimental medicine · 2023Pooled it
- Metformin enhances survival with immune checkpoint inhibitors in cancer patients: A meta-analysis.Oncology letters · 2026Article
- The impact of concomitant medications on treatment outcomes in patients with cancer receiving immune checkpoint inhibitors.Nature reviews. Cancer · 2026Review
- Host-related Determinants of Response to Immunotherapy in Non-small Cell Lung Cancer: The Interplay of Body Composition, Metabolism, Sex and Immune Regulation.Current oncology reports · 2025Review
- Time to metastasis as a prognostic factor in metastatic urothelial carcinoma: results from the ARON-2 study.Clinical & experimental metastasis · 2025Article
- Prognostic immunotherapy score (PIS) in patients with advanced urothelial carcinoma treated with pembrolizumab: real-world data and validation from ARON-2 dataset.Clinical & experimental metastasis · 2025Article
- Impact of concomitant use of proton pump inhibitors or cardiovascular medication on survival outcomes of patients with metastatic renal cell carcinoma treated with nivolumab.Clinical & experimental metastasis · 2025Article
- Sex as modifier of survival in patients with advanced urothelial cancer treated with pembrolizumab.Scientific reports · 2025Observational
- Concomitant medications in patients with metastatic urothelial carcinoma receiving enfortumab vedotin: real-world data from the ARON-2Clinical & experimental metastasis · 2025Article
- Real-Life Impact of Enfortumab Vedotin or Chemotherapy in the Sequential Treatment of Advanced Urothelial Carcinoma: The ARON-2 Retrospective Experience.Cancer medicine · 2025Observational
- Potential Roles of Long Non-coding RNAs in the Pathogenesis of Periodontitis: Inflammation Response, Immune Infiltration, Collagen Fibers Synthesis, and Bone Remodeling.Current medicinal chemistry · 2025Article
- Repurposing of Metformin to Improve Survival Outcomes in Patients With Upper Tract Urothelial Carcinoma.Cancer medicine · 2025Article
- The effect of concomitant drugs on oncological outcomes in patients treated with immunotherapy for metastatic urothelial carcinoma: a narrative review.Oncology research · 2025Review
- Angiotensin receptor blocker attacks armored and cold tumors and boosts immune checkpoint blockade.Journal for immunotherapy of cancer · 2024Article
- Pembrolizumab in Patients with Advanced Urothelial Carcinoma with ECOG Performance Status 2: A Real-World Study from the ARON-2 Project.Targeted oncology · 2024Article
- Radiotherapy plus pembrolizumab for advanced urothelial carcinoma: results from the ARON-2 real-world study.Scientific reports · 2024Article
- No difference in oncological outcomes and perioperative complications between patients with ESRD with unilateral and bilateral UTUC receiving radical nephroureterectomy.Scientific reports · 2024Article
- Recent developments and future directions of first-line systemic therapy combined with immunotherapy for advanced or metastatic urothelial carcinoma: a historical perspective on treatment evolution.International journal of clinical oncology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
92 authors at 20 institutions in 23 countries.
Ondřej Fiala *Department of Oncology and Radiotherapeutics, Faculty of Medicine and University Hospital Pilsen, Charles University, Alej Svobody 80, 304 60, Pilsen, Czech Republic. fialao@fnplzen.cz.
Sebastiano Buti *Department of Medicine and Surgery, University Hospital of Parma, Parma, Italy.
Hideki TakeshitaDepartment of Urology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
Yohei OkadaDepartment of Urology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
Francesco MassariMedical Oncology, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Via Albertoni - 15, Bologna, Italy.
Georgia Anguera PalaciosDepartment of Medical Oncology, Institutd' Investigació Biomèdica Sant Pau, Hospital de La Santa Creu I Sant Pau, Barcelona, Spain.
Michele DioneseOncology 1 Unit, Department of Oncology, Istituto Oncologico Veneto IOV IRCCS, 35128, Padua, Italy.
Sarah ScagliariniUOC Di Oncologia, Azienda Ospedaliera Di Rilievo Nazionale Cardarelli Di Napoli, Naples, Italy.
Thomas BüttnerDepartment of Urology, University Hospital Bonn (UKB), 53127, Bonn, Germany.
Giuseppe FornariniIRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Zin W MyintMarkey Cancer Center, University of Kentucky, Lexington, KY, 40536-0293, USA.
Luca GalliOncology Unit 2, University Hospital of Pisa, 56126, Pisa, Italy.
Vinicius Carrera SouzaHospital São Rafael Oncologia D'Or, Salvador, BA, Brazil.
Renate PichlerDepartment of Urology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.
Ugo De GiorgiDepartment of Medical Oncology, IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
María Natalia Gandur QuirogaLatin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Danielle GilbertUniversity of Colorado Cancer Center, Anschutz Medical Campus, Aurora, CO, USA.
Lazar PopovicOncology Institute of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
Enrique GrandeDepartment of Medical Oncology, MD Anderson Cancer Center Madrid, Madrid, Spain.
Giulia MammoneDepartment of Radiological, Oncological and Anatomo-Pathological Science, Sapienza University of Rome, Viale Regina Elena 324, 00185, Rome, Italy.
Rossana BerardiDepartment of Medical Oncology, Università Politecnica Delle Marche, AOU Ospedali Riuniti Delle Marche, Ancona, Italy.
Simon J CrabbSouthampton Experimental Cancer Medicine Centre, University of Southampton, Southampton, UK.
Javier Molina-CerrilloDepartment of Medical Oncology, Hospital Ramón Y Cajal, Madrid, Spain.
Marcelo FreitasLatin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Murilo LuzLatin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Roberto IacovelliOncologia Medica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
Fabio CalabròDepartment of Oncology, San Camillo Forlanini Hospital, Rome, Italy.
Deniz TuralDepartment of Medical Oncology, Bakirköy Dr. Sadi Konuk Training and Research Hospital, Zuhuratbaba District, Tevfik Saglam St. No: 11, Bakirkoy, Istanbul, Turkey.
Francesco AtzoriUnità Di Oncologia Medica, Azienda Ospedaliero Universitaria Di Cagliari, Cagliari, Italy.
Zsófia KüronyaDepartment of Genitourinary Medical Oncology and Clinical Pharmacology, National Institute of Oncology, Budapest, Hungary.
Rita ChiariUOC Oncologia, Azienda Ospedaliera Ospedali Riuniti Marche Nord, Fano, Italy.
Saul CamposLatin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Orazio CaffoMedical Oncology Unit, Santa Chiara Hospital, Trento, Italy.
André P FayLatin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Jakub KucharzDepartment of Uro-Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
Paolo Andrea ZucaliDepartment of Oncology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
José Augusto RinckLatin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Annalisa ZeppelliniNiguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
Diogo Assed BastosLatin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Gaetano AurilioMedical Oncology Division of Urogenital and Head and Neck Tumours, IEO, European Institute of Oncology IRCCS, Milan, Italy.
Augusto MotaLatin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Karine TrindadeLatin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Cinzia OrtegaDivision of Oncology, Institute for Cancer Research and Treatment, Asl Cn2 Alba-Brà, 12051, Alba-Brà, Italy.
Juan Pablo SadeInstituto Alexander Fleming, Buenos Aires, CABA, Argentina.
Mimma RizzoDivision of Medical Oncology, A.O.U. Consorziale Policlinico Di Bari, Piazza G. Cesare 11, 70124, Bari, Italy.
Nuno VauUrologic Oncology, Champalimaud Clinical Center, 1400-038, Lisbon, Portugal.
Patrizia GiannatempoDipartimento Di Oncologia Medica, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy.
Allan BarillasLatin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Fernando Sabino Marques MonteiroLatin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Breno DausterLatin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Carlo CattriniDepartment of Medical Oncology, "Maggiore Della Carità" University Hospital, 28100, Novara, Italy.
Lucas NogueiraLatin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Roni de Carvalho FernandesHospital Santa Casa de Sao Paulo, São Paulo, SP, Brazil.
Emmanuel SerontDepartment of Medical Oncology, Centre Hospitalier de Jolimont, Haine Saint Paul, Belgium.
Luís Garcia AceitunoLatin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Francesco GrilloneSOC Oncologia Medica, Azienda Ospedaliera "Pugliese -Ciaccio", Catanzaro, Italy.
Hernan Javier CutuliHospital Sirio Libanes, Buenos Aires, CABA, Argentina.
Mauricio FernandezLatin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Maria BassanelliMedical Oncology, 1-IRCCS Regina Elena National Cancer Institute, Rome, Italy.
Giandomenico RovielloDepartment of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy.
Halima AbahssainMedical Oncology Unit, National Institute of Oncology, Medicine and Pharmacy Faculty, Mohammed V University, Rabat, Morocco.
Giuseppe ProcopioDipartimento Di Oncologia Medica, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy.
Michele MilellaSection of Oncology, Department of Medicine, School of Medicine and Verona University Hospital Trust, University of Verona, Verona, Italy.
Jindrich KopeckyDepartment of Clinical Oncology and Radiotherapy, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic.
Angelo MartignettiUOC Oncologia Medica, Ospedale Dell'alta Val D'Elsa - Usl sud est Toscana Area Senese, Poggibonsi, Italy.
Carlo MessinaOncology Unit, A.R.N.A.S. Civico, Palermo, Italy.
Manuel CaitanoLatin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Eva InmanLatin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Ravindran KanesvaranNational Cancer Centre Singapore, Singapore, Republic of Singapore.
Daniel HerchenhornLatin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Daniele SantiniDepartment of Radiological, Oncological and Pathological Sciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
Ray MannehClinical Oncology, Sociedad de Oncología Y Hematología del Cesar, Valledupar, Colombia.
Renato BisonniUOC Oncologia Medica, Ospedale A. Murri, Fermo, Italy.
Roubini Zakopoulou2nd Propaedeutic Department of Internal Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece.
Alessandra MoscaDepartment of Oncology Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy.
Franco MorelliMedical Oncology Unit, Gemelli Molise Hospital, Università Cattolica del Sacro Cuore, Campobasso, Italy.
Fernando MalufHospital Beneficencia Portuguesa de São Paulo, São Paulo, SP, Brazil.
Andrey SoaresLatin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Fernando NunesLatin American Cooperative Oncology Group - LACOG, Porto Alegre, Brazil.
Alvaro PintoMedical Oncology Department, La Paz University Hospital, Madrid, Spain.
Anca ZguraDepartment of Oncology-Radiotherapy, Prof. Dr. Alexandru Trestioreanu Institute of Oncology, University of Medicine and Pharmacy, Bucharest, Romania.
Lorena IncorvaiaDepartment of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
Jawaher AnsariMedical Oncology, Tawam Hospital, Al Ain, United Arab Emirates.
Ignacio Ortego ZabalzaDepartment of Medical Oncology, MD Anderson Cancer Center Madrid, Madrid, Spain.
Johannes LandmesserKlinik Für Urologie, Ratzeburger Allee 160, 23538, Lübeck, Germany.
Alessandro RizzoStruttura Semplice Dipartimentale Di Oncologia Medica Per La Presa in Carico Globale del Paziente Oncologico "Don Tonino Bello", I.R.C.C.S. Istituto Tumori "Giovanni Paolo II", Viale Orazio Flacco 65, 70124, Bari, Italy.
Veronica MollicaMedical Oncology, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Via Albertoni - 15, Bologna, Italy.
Giulia SorgentoniOncology Unit, Macerata Hospital, Via Santa Lucia 2, 62100, Macerata, Italy.
Nicola BattelliOncology Unit, Macerata Hospital, Via Santa Lucia 2, 62100, Macerata, Italy.
Camillo PortaInterdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy.
Joaquim Bellmunt *Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Matteo Santoni *Oncology Unit, Macerata Hospital, Via Santa Lucia 2, 62100, Macerata, Italy.
Ospedale di MacerataAzienda USL di Bologna · ITHospital Israelita Albert Einstein · BRHospital São Rafael · BRMD Anderson Cancer Center Madrid · ESSocial Insurance Saitama Chuo Hospital · JPAC Camargo Hospital · BRAgostino Gemelli University Polyclinic · ITAzienda di Rilievo Nazionale ed Alta Specializzazione · ITAzienda Ospedaliera Ospedale Maggiore · ITAzienda Ospedaliera Pugliese Ciaccio · ITAzienda Ospedaliera Universitaria Pisana · ITAzienda Ospedaliero-Universitaria Cagliari · ITAzienda Sanitaria Locale CN2 · ITAzienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda · ITBakırköy Dr.Sadi Konuk Eğitim ve Araştırma Hastanesi · TRCandiolo Cancer Institute · ITCarlo Forlanini Hospital · ITCentro de Epilepsia y Neurocirugía Funcional · GTCentro de Pesquisas Oncológicas · BR
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundConcomitant medications may potentially affect the outcome of cancer patients. In this sub-analysis of the ARON-2 real-world study (NCT05290038), we aimed to assess the impact of concomitant use of proton pump inhibitors (PPI), statins, or metformin on outcome of patients with metastatic urothelial cancer (mUC) receiving second-line pembrolizumab.
methodsWe collected data from the hospital medical records of patients with mUC treated with pembrolizumab as second-line therapy at 87 institutions from 22 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate. We carried out a survival analysis by a Cox regression model.
resultsA total of 802 patients were eligible for this retrospective study; the median follow-up time was 15.3 months. PPI users compared to non-users showed inferior PFS (4.5 vs. 7.2 months, p = 0.002) and OS (8.7 vs. 14.1 months, p < 0.001). Concomitant PPI use remained a significant predictor of PFS and OS after multivariate Cox analysis. The use of statins or metformin was not associated with response or survival.
conclusionsOur study results suggest a significant prognostic impact of concomitant PPI use in mUC patients receiving pembrolizumab in the real-world context. The mechanism of this interaction warrants further elucidation.
Indexed as
Carcinoma, Transitional CellHydroxymethylglutaryl-CoA Reductase InhibitorsMetforminUrinary Bladder NeoplasmsAntibodies, Monoclonal, HumanizedHumansProton Pump InhibitorsRetrospective StudiesAntibodies, Monoclonal, HumanizedHydroxymethylglutaryl-CoA Reductase InhibitorsMetforminpembrolizumabProton Pump InhibitorsARON-2 studyImmunotherapyMetforminProton pump inhibitorsStatinsUrothelial cancer
Identifiers
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Textmetadata
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Registered trials
NCT05290038ClinicalTrials.gov
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 Socratic graph.