Importance Immune 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. Objectives To evaluate the association of PD-L1 with response rate and overall survival among patients with mUC treated with ICIs. Data Sources PubMed, 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 Selection Two 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 Synthesis The 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 Measures Primary 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. Results A 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 < .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 < .001) when ICIs were administered. PD-L1 is not likely to be a predictive biomarker of ICI response. Conclusions and Relevance This 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.
Significance of PD-L1 in Metastatic Urothelial Carcinoma Treated With Immune Checkpoint Inhibitors / Maiorano, Brigida Anna; Di Maio, Massimo; Cerbone, Linda; Maiello, Evaristo; Procopio, Giuseppe; Roviello, Giandomenico; Null, Null; Accettura, Caterina; Aieta, Michele; Alberti, Martina; Aliprandi, Marta; Altavilla, Amelia; Antonuzzo, Lorenzo; Artemi, Adele; Arundine, Dario; Astore, Serena; Attademo, Laura; Atzori, Francesco; Aurilio, Gaetano; Azzariti, Amalia; Baciarello, Giulia; Baier, Susanne; Baldazzi, Valentina; Banna, Giuseppe L; Barile, Carmen; Barra, Salvina; Barraco, Chiara; Basile, Debora; Bassanelli, Maria; Basso, Umberto; Bauckneht, Matteo; Bearz, Alessandra; Bellia, Salvatore R; Benedetti, Benedetta; Berardi, Rossana; Bergamini, Marco; Bersanelli, Melissa; Bertoni, Maria; Bianchi, Emanuela; Biasini, Claudia; Bidin, Livia; Bimbatti, Davide; Bleve, Sara; Boccardo, Francesco; Bolzacchini, Elena; Bonato, Adele; Bonomi, Lucia; Bordonaro, Sebastiano; Borghesi, Marco; Bortolus, Roberto; Bortot, Lucia; Bosso, Davide; Bottiglieri, Achille; Bozza, Giovanni; Bregni, Marco; Brighi, Nicole; Bronte, Enrico; Bruni, Alessio; Bruno, Michele; Buffoni, Martina; Buonerba, Luciana; Buonerba, Carlo; Buti, Sebastiano; Buttigliero, Consuelo; Cadau, Jessica; Caffo, Orazio; Calabrò, Fabio; Calvani, Nicola; Campobasso, Davide; Capacci, Samanta; Capitanio, Umberto; Caponnetto, Salvatore R; Carella, Claudia; Carlini, Paolo; Carrozza, Francesco; Cartenì, Giacomo; Caruso, Davide; Casadei, Chiara; Catalano, Fabio; Catalano, Martina; Cattrini, Carlo; Cavasin, Nicolò; Cavo, Alessia; Cecchi, Luigi G; Cecere, Sabrina C; Cerbone, Linda; Ceresoli, Giovanni L; Chiari, Rita; Chiellino, Silvia; Chiuri, Vincenzo E; Ciccarelli, Stefano; Cicero, Giuseppe L; Cinausero, Marika; Citarella, Fabrizio; Claps, Melanie; Cocorocchio, Emilia; Conteduca, Vincenza; Coppola, Elisabetta; Cordua, Nadia; Cossu Rocca, Maria; Courthod, Giulia; Cremante, Malvina; Cullurà, Daniela; Cursano, Maria C; D'Ostilio, Nicola; Dalla Volta, Alberto; Damassi, Alessandra; Daniele, Bruno; De Giorgi, Ugo FF; De Lisa, Mariagrazia; De Lisi, Delia; De Summa, Simona; De Vivo, Rocco; Debonis, Silvia A; Del Re, Marzia; Depetris, Ilaria; Di Civita, Mattia A; Di Costanzo, Fabrizio; Di Francesco, Simona; Di Girolamo, Stefania; Di Lorenzo, Giuseppe; Di Maio, Massimo; Di Napoli, Marilena; Di Rocco, Roberta; Di Tullio, Piergiorgio; Dinota, Angelo; Dionese, Michele; Donati, Donatella; Doni, Laura; Doronzo, Antonio; Dri, Arianna; Ermacora, Paola; Evangelista, Laura; Fanelli, Martina; Farè, Elena; Farnesi, Azzurra; Farolfi, Alberto; Febbraro, Antonio; Fedele, Palma; Federico, Piera; Filaci, Gilberto; Filippi, Roberto; Filograna, Alessia; Foderaro, Simone; Fontana, Antonella; Formisano, Luigi; Fornarini, Giuseppe; Francini, Edoardo; Franzese, Ciro; Fratino, Lucia; Galanti, Daniele; Galli, Luca; Gamba, Teresa; Gambale, Elisabetta; Garattini, Silvio K; Garibaldi, Elisabetta; Gasparro, Donatello; Gentile, Anna L; Germano, Domenico; Gernone, Angela; Ghilardi, Laura; Giannatempo, Patrizia; Gianni, Caterina; Gianotti, Emilia; Giorgione, Roberta; Giudice, Giulia C; Giunta, Emilio F; Gridelli, Cesare; Grillone, Francesco; Guadalupi, Valentina; Gualtieri, Simona; Guarneri, Alessia S; Guglielmo, Priscilla; Hamzaj, Alketa; Hamzaj, Afete; Iaia, Maria L; Ierinò, Debora; Incorvaia, Lorena; Ingenito, Concetta; Inzerilli, Nicola; Jubran, Salim; Kinspergher, Stefania; La Camera, Antonella; La Russa, Francesca; Lai, Eleonora; Lancia, Federica; Landriscina, Matteo; Lanfranchi, Francesco; Latteri, Fiorenza; Lenci, Edoardo; Lipari, Helga MA; Llaja Obispo, Migual A; Lo Vecchio, Monica; Lombardo, Valentina N; Lombardo, Laura; Luciani, Andrea; Macerelli, Marianna; Maffezzoli, Michele; Maines, Francesca; Maiorano, Brigida A; Malgeri, Andrea; Marinelli, Daniele; Maruzzo, Marco; Masini, Cristina; Massi, Daiana; Mastrorosa, Alessandro; Mattana, Alvise; Mencoboni, Manlio; Mennitto, Alessia; Mercinelli, Chiara; Messina, Carlo; Messina, Marco; Migliaccio, Fortuna; Migliari, Marco; Montagna, Benedetta; Montanari, Daniela; Morelli, Anna M; Morelli, Franco; Moroso, Stefano; Mosca, Alessandra; Mucciarini, Claudia; Hernandez, Fernando M; Murgia, Viviana; Murianni, Veronica; Murru, Maura; Muto, Andrea; Naglieri, Emanuele; Nasso, Cecilia; Nicodemo, Maurizio; Nolè, Franco; Orlando, Valentina; Ortega, Cinzia; Paccagnella, Elisabetta; Pacelli, Roberto; Palazzo, Antonio; Palesandro, Erica; Pantano, Francesco; Paolieri, Federico; Pappagallo, Maria N; Pappalardo, Laura; Pasqualini, Antonella; Passalacqua, Rodolfo; Passarelli, Anna; Pecoraro, Giovanna; Pedrazzoli, Paolo; Pelin, Giulia M; Pellino, Antonio; Pepe, Alessio; Perna, Marco; Perrino, Matteo; Perrone, Francesco; Perrucci, Bruno; Persano, Mara; Piancastelli, Alessandra; Picciotto, Maria; Pierantoni, Francesco; Pignata, Sandro; Pilato, Brunella; Piras, Margherita; Pireddu, Annagrazia; Pisano, Chiara; Pisano, Carmela; Piscazzi, Annamaria; Pisconti, Salvatore R; Pisino, Marco; Pitrè, Alessandra; Poeta, Maria L; Pompella, Luca; Poti, Giulia; Prati, Veronica; Procopio, Giuseppe; Puglia, Livio; Razzini, Giorgia; Rebuzzi, Sara E; Recine, Federica; Rescigno, Pasquale; Ribera, Dario; Ricotta, Riccardo; Rizzo, Alessio; Rizzo, Mimma; Roberto, Michela; Rollo, Luisa; Rossetti, Sabrina; Rossi, Virginia; Rossi, Ernesto; Rossi, Lorena; Rosti, Giovanni; Roviello, Giandomenico; Russi, Elvio G; Salesi, Nello; Salfi, Alessia; Sammarco, Enrico; Sanguedolce, Francesca; Sansi, Camilla; Santamaria, Fiorenza; Santini, Daniele; Santoni, Matteo; Sartori, Donata; Sartragno, Camilla; Sava, Teodoro; Sbrana, Andrea; Scagliarini, Sarah; Scala, Stefania; Scandurra, Giuseppa; Scattolin, Daniela; Schepisi, Giuseppe; Schettino, Clorinda; Schinzari, Giovanni; Secondino, Simona; Sepe, Pierangela; Serra, Riccardo; Signori, Alessio; Silvestro, Giustino; Sirotovà, Zuzana; Sorarù, Mariella; Soto Parra, Hector; Spinelli, Gian P; Stellato, Marco; Stumbo, Luciano; Tagliaferri, Pierosandro; Tambaro, Rosa; Tamberi, Stefano; Testi, Irene; Toma, Ilaria; Tomasino, Mirko; Tommasi, Stefania; Tortora, Vincenzo; Tortorella, Anna; Toscani, Ilaria; Tralongo, Paolo; Triolo, Renza; Tucci, Marcello; Urban, Susanna; Urso, Luca; Valsecchi, Anna A; Veccia, Antonello; Vela, Chiara; Ventriglia, Jole; Verde, Antonio; Verzoni, Elenza; Vignani, Francesca; Vitale, Maria G; Vittimberga, Isabella; Zacchi, Francesca; Zago, Giulia; Zagonel, Vittorina; Zanardi, Elisa; Zara, Diego; Zeppellini, Annalisa; Zonno, Antonia; Zucali, Paola A; Zumstein, Lucrezia. - In: JAMA NETWORK OPEN. - ISSN 2574-3805. - 7:3(2024). [10.1001/jamanetworkopen.2024.1215]
Significance of PD-L1 in Metastatic Urothelial Carcinoma Treated With Immune Checkpoint Inhibitors
Buti, SebastianoMembro del Collaboration Group
;Giudice, Giulia CMembro del Collaboration Group
;Maffezzoli, MicheleMembro del Collaboration Group
;Testi, IreneMembro del Collaboration Group
;
2024-01-01
Abstract
Importance Immune 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. Objectives To evaluate the association of PD-L1 with response rate and overall survival among patients with mUC treated with ICIs. Data Sources PubMed, 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 Selection Two 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 Synthesis The 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 Measures Primary 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. Results A 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 < .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 < .001) when ICIs were administered. PD-L1 is not likely to be a predictive biomarker of ICI response. Conclusions and Relevance This 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.