Significance of PD-L1 in Metastatic Urothelial Carcinoma Treated With Immune Checkpoint Inhibitors
Articolo
Data di Pubblicazione:
2024
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..
Tipologia CRIS:
1.1 Articolo in rivista
Elenco autori:
Maiorano, Brigida Anna, Di Maio, Massimo, ; Linda, Cerbone,, ; Evaristo, Maiello,, ; Giuseppe, Procopio,, ; Giandomenico, Roviello,, ; Null, Null,, ; Caterina, Accettura,, ; Michele, Aieta,, ; Martina, Alberti,, ; Marta, Aliprandi,, ; Amelia, Altavilla,, ; Lorenzo, Antonuzzo,, ; Adele, Artemi,, ; Dario, Arundine,, ; Serena, Astore,, ; Laura, Attademo,, ; Francesco, Atzori,, ; Gaetano, Aurilio,, ; Amalia, Azzariti,, ; Giulia, Baciarello,, ; Susanne, Baier,, ; Valentina, Baldazzi,, ; L, Banna, Giuseppe, ; Carmen, Barile,, ; Salvina, Barra,, ; Chiara, Barraco,, ; Debora, Basile,, ; Maria, Bassanelli,, ; Umberto, Basso,, ; Matteo, Bauckneht,, ; Alessandra, Bearz,, ; R, Bellia, Salvatore, ; Benedetta, Benedetti,, ; Rossana, Berardi,, ; Marco, Bergamini,, ; Melissa, Bersanelli,, ; Maria, Bertoni,, ; Emanuela, Bianchi,, ; Claudia, Biasini,, ; Livia, Bidin,, ; Davide, Bimbatti,, ; Sara, Bleve,, ; Francesco, Boccardo,, ; Elena, Bolzacchini,, ; Adele, Bonato,, ; Lucia, Bonomi,, ; Sebastiano, Bordonaro,, ; Marco, Borghesi,, ; Roberto, Bortolus,, ; Lucia, Bortot,, ; Davide, Bosso,, ; Achille, Bottiglieri,, ; Giovanni, Bozza,, ; Marco, Bregni,, ; Nicole, Brighi,, ; Enrico, Bronte,, ; Alessio, Bruni,, ; Michele, Bruno,, ; Martina, Buffoni,, ; Luciana, Buonerba,, ; Carlo, Buonerba,, ; Sebastiano, Buti,, ; Consuelo, Buttigliero,, ; Jessica, Cadau,, ; Orazio, Caffo,, ; Fabio, Calabrò,, ; Nicola, Calvani,, ; Davide, Campobasso,, ; Samanta, Capacci,, ; Umberto, Capitanio,, ; Caponnetto, Salvatore; Claudia, Carella,, ; Paolo, Carlini,, ; Francesco, Carrozza,, ; Giacomo, Cartenì,, ; Davide, Caruso,, ; Chiara, Casadei,, ; Fabio, Catalano,, ; Martina, Catalano,, ; Carlo, Cattrini,, ; Nicolò, Cavasin,, ; Alessia, Cavo,, ; G, Cecchi, Luigi, ; C, Cecere, Sabrina, ; Linda, Cerbone,, ; L, Ceresoli, Giovanni, ; Rita, Chiari,, ; Silvia, Chiellino,, ; E, Chiuri, Vincenzo, ; Stefano, Ciccarelli,, ; L, Cicero, Giuseppe, ; Marika, Cinausero,, ; Fabrizio, Citarella,, ; Melanie, Claps,, ; Emilia, Cocorocchio,, ; Vincenza, Conteduca,, ; Elisabetta, Coppola,, ; Nadia, Cordua,, ; Maria, Cossu Rocca,, ; Giulia, Courthod,, ; Malvina, Cremante,, ; Daniela, Cullurà,, ; C, Cursano, Maria, ; Nicola, D'Ostilio,, ; Alberto, Dalla Volta,, ; Alessandra, Damassi,, ; Bruno, Daniele,, ; Ff, De Giorgi, Ugo, ; Mariagrazia, De Lisa,, ; Delia, De Lisi,, ; Simona, De Summa,, ; Rocco, De Vivo,, ; A, Debonis, Silvia, ; Marzia, Del Re,, ; Ilaria, Depetris,, ; A, Di Civita, Mattia, ; Fabrizio, Di Costanzo,, ; Simona, Di Francesco,, ; Stefania, Di Girolamo,, ; Giuseppe, Di Lorenzo,, ; Massimo, Di Maio,, ; Marilena, Di Napoli,, ; Roberta, Di Rocco,, ; Piergiorgio, Di Tullio,, ; Angelo, Dinota,, ; Michele, Dionese,, ; Donatella, Donati,, ; Laura, Doni,, ; Antonio, Doronzo,, ; Arianna, Dri,, ; Paola, Ermacora,, ; Laura, Evangelista,, ; Martina, Fanelli,, ; Elena, Farè,, ; Azzurra, Farnesi,, ; Alberto, Farolfi,, ; Antonio, Febbraro,, ; Palma, Fedele,, ; Piera, Federico,, ; Gilberto, Filaci,, ; Roberto, Filippi,, ; Alessia, Filograna,, ; Simone, Foderaro,, ; Antonella, Fontana,, ; Luigi, Formisano,, ; Giuseppe, Fornarini,, ; Edoardo, Francini,, ; Ciro, Franzese,, ; Lucia, Fratino,, ; Daniele, Galanti,, ; Luca, Galli,, ; Teresa, Gamba,, ; Elisabetta, Gambale,, ; K, Garattini, Silvio, ; Elisabetta, Garibaldi,, ; Donatello, Gasparro,, ; L, Gentile, Anna, ; Domenico, Germano,, ; Angela, Gernone,, ; Laura, Ghilardi,, ; Patrizia, Giannatempo,, ; Caterina, Gianni,, ; Emilia, Gianotti,, ; Roberta, Giorgione,, ; C, Giudice, Giulia, ; F, Giunta, Emilio, ; Cesare, Gridelli,, ; Francesco, Grillone,, ; Valentina, Guadalupi,, ; Simona, Gualtieri,, ; S, Guarneri, Alessia, ; Priscilla, Guglielmo,, ; Alketa, Hamzaj,, ; Afete, Hamzaj,, ; L, Iaia, Maria, ; Debora, Ierinò,, ; Lorena, Incorvaia,, ; Concetta, Ingenito,, ; Nicola, Inzerilli,, ; Salim, Jubran,, ; Stefania, Kinspergher,, ; Antonella, La Camera,, ; Francesca, La Russa,, ; Eleonora, Lai,, ; Federica, La
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