Significance of PD-L1 in Metastatic Urothelial Carcinoma Treated With Immune Checkpoint Inhibitors-Reference-Cited by-同舟云学术

Significance of PD-L1 in Metastatic Urothelial Carcinoma Treated With Immune Checkpoint Inhibitors

Published:2024-03-06 Issue:3 Volume:7 Page:e241215
ISSN:2574-3805
Container-title:JAMA Network Open
language:en
Short-container-title:JAMA Netw Open

Author:

Maiorano Brigida Anna¹,Di Maio Massimo²³,Cerbone Linda⁴,Maiello Evaristo¹,Procopio Giuseppe⁵,Roviello Giandomenico⁶, ,Accettura Caterina⁷,Aieta Michele⁷,Alberti Martina⁷,Aliprandi Marta⁷,Altavilla Amelia⁷,Antonuzzo Lorenzo⁷,Artemi Adele⁷,Arundine Dario⁷,Astore Serena⁷,Attademo Laura⁷,Atzori Francesco⁷,Aurilio Gaetano⁷,Azzariti Amalia⁷,Baciarello Giulia⁷,Baier Susanne⁷,Baldazzi Valentina⁷,Banna Giuseppe L⁷,Barile Carmen⁷,Barra Salvina⁷,Barraco Chiara⁷,Basile Debora⁷,Bassanelli Maria⁷,Basso Umberto⁷,Bauckneht Matteo⁷,Bearz Alessandra⁷,Bellia Salvatore R⁷,Benedetti Benedetta⁷,Berardi Rossana⁷,Bergamini Marco⁷,Bersanelli Melissa⁷,Bertoni Maria⁷,Bianchi Emanuela⁷,Biasini Claudia⁷,Bidin Livia⁷,Bimbatti Davide⁷,Bleve Sara⁷,Boccardo Francesco⁷,Bolzacchini Elena⁷,Bonato Adele⁷,Bonomi Lucia⁷,Bordonaro Sebastiano⁷,Borghesi Marco⁷,Bortolus Roberto⁷,Bortot Lucia⁷,Bosso Davide⁷,Bottiglieri Achille⁷,Bozza Giovanni⁷,Bregni Marco⁷,Brighi Nicole⁷,Bronte Enrico⁷,Bruni Alessio⁷,Bruno Michele⁷,Buffoni Martina⁷,Buonerba Luciana⁷,Buonerba Carlo⁷,Buti Sebastiano⁷,Buttigliero Consuelo⁷,Cadau Jessica⁷,Caffo Orazio⁷,Calabrò Fabio⁷,Calvani Nicola⁷,Campobasso Davide⁷,Capacci Samanta⁷,Capitanio Umberto⁷,Caponnetto Salvatore R⁷,Carella Claudia⁷,Carlini Paolo⁷,Carrozza Francesco⁷,Cartenì Giacomo⁷,Caruso Davide⁷,Casadei Chiara⁷,Catalano Fabio⁷,Catalano Martina⁷,Cattrini Carlo⁷,Cavasin Nicolò⁷,Cavo Alessia⁷,Cecchi Luigi G⁷,Cecere Sabrina C⁷,Cerbone Linda⁷,Ceresoli Giovanni L⁷,Chiari Rita⁷,Chiellino Silvia⁷,Chiuri Vincenzo E⁷,Ciccarelli Stefano⁷,Cicero Giuseppe L⁷,Cinausero Marika⁷,Citarella Fabrizio⁷,Claps Melanie⁷,Cocorocchio Emilia⁷,Conteduca Vincenza⁷,Coppola Elisabetta⁷,Cordua Nadia⁷,Cossu Rocca Maria⁷,Courthod Giulia⁷,Cremante Malvina⁷,Cullurà Daniela⁷,Cursano Maria C⁷,D'Ostilio Nicola⁷,Dalla Volta Alberto⁷,Damassi Alessandra⁷,Daniele Bruno⁷,De Giorgi Ugo FF⁷,De Lisa Mariagrazia⁷,De Lisi Delia⁷,De Summa Simona⁷,De Vivo Rocco⁷,Debonis Silvia A⁷,Del Re Marzia⁷,Depetris Ilaria⁷,Di Civita Mattia A⁷,Di Costanzo Fabrizio⁷,Di Francesco Simona⁷,Di Girolamo Stefania⁷,Di Lorenzo Giuseppe⁷,Di Maio Massimo⁷,Di Napoli Marilena⁷,Di Rocco Roberta⁷,Di Tullio Piergiorgio⁷,Dinota Angelo⁷,Dionese Michele⁷,Donati Donatella⁷,Doni Laura⁷,Doronzo Antonio⁷,Dri Arianna⁷,Ermacora Paola⁷,Evangelista Laura⁷,Fanelli Martina⁷,Farè Elena⁷,Farnesi Azzurra⁷,Farolfi Alberto⁷,Febbraro Antonio⁷,Fedele Palma⁷,Federico Piera⁷,Filaci Gilberto⁷,Filippi Roberto⁷,Filograna Alessia⁷,Foderaro Simone⁷,Fontana Antonella⁷,Formisano Luigi⁷,Fornarini Giuseppe⁷,Francini Edoardo⁷,Franzese Ciro⁷,Fratino Lucia⁷,Galanti Daniele⁷,Galli Luca⁷,Gamba Teresa⁷,Gambale Elisabetta⁷,Garattini Silvio K⁷,Garibaldi Elisabetta⁷,Gasparro Donatello⁷,Gentile Anna L⁷,Germano Domenico⁷,Gernone Angela⁷,Ghilardi Laura⁷,Giannatempo Patrizia⁷,Gianni Caterina⁷,Gianotti Emilia⁷,Giorgione Roberta⁷,Giudice Giulia C⁷,Giunta Emilio F⁷,Gridelli Cesare⁷,Grillone Francesco⁷,Guadalupi Valentina⁷,Gualtieri Simona⁷,Guarneri Alessia S⁷,Guglielmo Priscilla⁷,Hamzaj Alketa⁷,Hamzaj Afete⁷,Iaia Maria L⁷,Ierinò Debora⁷,Incorvaia Lorena⁷,Ingenito Concetta⁷,Inzerilli Nicola⁷,Jubran Salim⁷,Kinspergher Stefania⁷,La Camera Antonella⁷,La Russa Francesca⁷,Lai Eleonora⁷,Lancia Federica⁷,Landriscina Matteo⁷,Lanfranchi Francesco⁷,Latteri Fiorenza⁷,Lenci Edoardo⁷,Lipari Helga MA⁷,Llaja Obispo Migual A⁷,Lo Vecchio Monica⁷,Lombardo Valentina N⁷,Lombardo Laura⁷,Luciani Andrea⁷,Macerelli Marianna⁷,Maffezzoli Michele⁷,Maines Francesca⁷,Maiorano Brigida A⁷,Malgeri Andrea⁷,Marinelli Daniele⁷,Maruzzo Marco⁷,Masini Cristina⁷,Massi Daiana⁷,Mastrorosa Alessandro⁷,Mattana Alvise⁷,Mencoboni Manlio⁷,Mennitto Alessia⁷,Mercinelli Chiara⁷,Messina Carlo⁷,Messina Marco⁷,Migliaccio Fortuna⁷,Migliari Marco⁷,Montagna Benedetta⁷,Montanari Daniela⁷,Morelli Anna M⁷,Morelli Franco⁷,Moroso Stefano⁷,Mosca Alessandra⁷,Mucciarini Claudia⁷,Hernandez Fernando M⁷,Murgia Viviana⁷,Murianni Veronica⁷,Murru Maura⁷,Muto Andrea⁷,Naglieri Emanuele⁷,Nasso Cecilia⁷,Nicodemo Maurizio⁷,Nolè Franco⁷,Orlando Valentina⁷,Ortega Cinzia⁷,Paccagnella Elisabetta⁷,Pacelli Roberto⁷,Palazzo Antonio⁷,Palesandro Erica⁷,Pantano Francesco⁷,Paolieri Federico⁷,Pappagallo Maria N⁷,Pappalardo Laura⁷,Pasqualini Antonella⁷,Passalacqua Rodolfo⁷,Passarelli Anna⁷,Pecoraro Giovanna⁷,Pedrazzoli Paolo⁷,Pelin Giulia M⁷,Pellino Antonio⁷,Pepe Alessio⁷,Perna Marco⁷,Perrino Matteo⁷,Perrone Francesco⁷,Perrucci Bruno⁷,Persano Mara⁷,Piancastelli Alessandra⁷,Picciotto Maria⁷,Pierantoni Francesco⁷,Pignata Sandro⁷,Pilato Brunella⁷,Piras Margherita⁷,Pireddu Annagrazia⁷,Pisano Chiara⁷,Pisano Carmela⁷,Piscazzi Annamaria⁷,Pisconti Salvatore R⁷,Pisino Marco⁷,Pitrè Alessandra⁷,Poeta Maria L⁷,Pompella Luca⁷,Poti Giulia⁷,Prati Veronica⁷,Procopio Giuseppe⁷,Puglia Livio⁷,Razzini Giorgia⁷,Rebuzzi Sara E⁷,Recine Federica⁷,Rescigno Pasquale⁷,Ribera Dario⁷,Ricotta Riccardo⁷,Rizzo Alessio⁷,Rizzo Mimma⁷,Roberto Michela⁷,Rollo Luisa⁷,Rossetti Sabrina⁷,Rossi Virginia⁷,Rossi Ernesto⁷,Rossi Lorena⁷,Rosti Giovanni⁷,Roviello Giandomenico⁷,Russi Elvio G⁷,Salesi Nello⁷,Salfi Alessia⁷,Sammarco Enrico⁷,Sanguedolce Francesca⁷,Sansi Camilla⁷,Santamaria Fiorenza⁷,Santini Daniele⁷,Santoni Matteo⁷,Sartori Donata⁷,Sartragno Camilla⁷,Sava Teodoro⁷,Sbrana Andrea⁷,Scagliarini Sarah⁷,Scala Stefania⁷,Scandurra Giuseppa⁷,Scattolin Daniela⁷,Schepisi Giuseppe⁷,Schettino Clorinda⁷,Schinzari Giovanni⁷,Secondino Simona⁷,Sepe Pierangela⁷,Serra Riccardo⁷,Signori Alessio⁷,Silvestro Giustino⁷,Sirotovà Zuzana⁷,Sorarù Mariella⁷,Soto Parra Hector⁷,Spinelli Gian P⁷,Stellato Marco⁷,Stumbo Luciano⁷,Tagliaferri Pierosandro⁷,Tambaro Rosa⁷,Tamberi Stefano⁷,Testi Irene⁷,Toma Ilaria⁷,Tomasino Mirko⁷,Tommasi Stefania⁷,Tortora Vincenzo⁷,Tortorella Anna⁷,Toscani ilaria⁷,Tralongo Paolo⁷,Triolo Renza⁷,Tucci Marcello⁷,Urban Susanna⁷,Urso Luca⁷,Valsecchi Anna A⁷,Veccia Antonello⁷,Vela Chiara⁷,Ventriglia Jole⁷,Verde Antonio⁷,Verzoni Elenza⁷,Vignani Francesca⁷,Vitale Maria G⁷,Vittimberga Isabella⁷,Zacchi Francesca⁷,Zago Giulia⁷,Zagonel Vittorina⁷,Zanardi Elisa⁷,Zara Diego⁷,Zeppellini Annalisa⁷,Zonno Antonia⁷,Zucali Paola A⁷,Zumstein Lucrezia⁷

Affiliation:

1. Oncology Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

2. Oncology Department, University of Turin, Turin, Italy

3. Medical Oncology 1, AOU Città della Salute e della Scienza, Molinette Hospital, Turin, Italy

4. Oncology Unit, San Camillo Forlanini Hospital, Rome, Italy

5. Unit of Genito-Urinary Medical Oncology, IRCCS Foundation Istituto Nazionale dei Tumori, Milan, Italy

6. Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy

7. for the MeetURO Group

Abstract

ImportanceImmune checkpoint inhibitors (ICIs) have broadened the metastatic urothelial carcinoma (mUC) therapeutic scenario. The association of programmed death ligand 1 (PD-L1) with response and survival in patients treated with ICIs is still controversial.ObjectivesTo evaluate the association of PD-L1 with response rate and overall survival among patients with mUC treated with ICIs.Data SourcesPubMed, Embase, American Society of Clinical Oncology and European Society for Medical Oncology Meeting Libraries, and Web of Science were searched up to December 10, 2023.Study SelectionTwo authors independently screened the studies. Included studies were randomized and nonrandomized clinical trials enrolling patients with mUC receiving ICIs with available overall survival (OS), progression-free survival (PFS), or overall response rate (ORR) data, separated between patients with PD-L1–positive and –negative tumors.Data Extraction and SynthesisThe Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. Two reviewers independently extracted data. Fixed- or random-effects models were used depending on the heterogeneity among the studies.Main Outcomes and MeasuresPrimary outcomes were odds ratios (ORs) for ORR and hazard ratios (HRs) for OS, comparing patients with PD-L1–positive tumors and patients with PD-L1–negative tumors. Secondary outcomes were the PFS HR between patients with PD-L1–positive and –negative tumors and OS HR between ICI arms and non-ICI arms of only randomized clinical trials.ResultsA total of 14 studies were selected, comprising 5271 patients treated with ICIs (2625 patients had PD-L1–positive tumors). The ORR was 13.8% to 78.6% in patients with PD-L1–positive tumors and 5.1% to 63.2% in patients with PD-L1–negative tumors, with an association between PD-L1 status and ORR favoring patients with PD-L1–positive tumors (OR, 1.94; 95% CI, 1.47-2.56; P &lt; .001). Median OS ranged from 8.4 to 24.1 months in patients with PD-L1–positive tumors and from 6.0 to 19.1 months in patients with PD-L1–negative tumors. The pooled HR showed a significant reduction for patients with PD-L1–positive tumors compared with those with PD-L1–negative tumors in the risk of death (HR, 0.71; 95% CI, 0.57-0.89; P = .003) and risk of progression (HR, 0.55; 95% CI, 0.44-0.69; P &lt; .001) when ICIs were administered. PD-L1 is not likely to be a predictive biomarker of ICI response.Conclusions and RelevanceThis systematic review and meta-analysis suggests that PD-L1 expression is associated with improved ORR, OS, and PFS for patients with mUC who receive ICIs, but it is unlikely to be useful as a predictive biomarker. Developing predictive biomarkers is essential to select patients most likely to benefit from ICIs and avoid toxic effects and financial burden with these agents.

Publisher

American Medical Association (AMA)

Link

https://jamanetwork.com/journals/jamanetworkopen/articlepdf/2815767/maiorano_2024_oi_240074_1708699219.17392.pdf

Reference49 articles.

1. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.;Sung;CA Cancer J Clin,2021

2. Bladder cancer incidence and mortality: a global overview and recent trends.;Antoni;Eur Urol,2017

3. The 2021 updated European Association of Urology guidelines on metastatic urothelial carcinoma.;Cathomas;Eur Urol,2022

4. Immune-checkpoint inhibitors in advanced bladder cancer: seize the day.;Maiorano;Biomedicines,2022

5. PD-1 and its ligands in tolerance and immunity.;Keir;Annu Rev Immunol,2008

Cited by 3 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Novel therapeutic regimens in previously untreated metastatic urothelial carcinoma: A systematic review and bayesian network meta-analysis;Urologic Oncology: Seminars and Original Investigations;2024-11

2. Mechanistic Insights into the Successful Development of Combination Therapy of Enfortumab Vedotin and Pembrolizumab for the Treatment of Locally Advanced or Metastatic Urothelial Cancer;Cancers;2024-09-04

3. Construction and validation of a prognostic model for bladder cancer based on disulfidptosis-related lncRNAs;Medicine;2024-07-05