biostudies-literatureUnknown7(3)Maiorano BA<h4>Importance</h4>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.<h4>Objectives</h4>To evaluate the association of PD-L1 with response rate and overall survival among patients with mUC treated with ICIs.<h4>Data sources</h4>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.<h4>Study selection</h4>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.<h4>Data extraction and synthesis</h4>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.<h4>Main outcomes and measures</h4>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.<h4>Results</h4>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.<h4>Conclusions and relevance</h4>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.JAMA network opene241215https://www.ebi.ac.uk/biostudies/studies/S-EPMC10918499biostudies-literatureSignificance of PD-L1 in Metastatic Urothelial Carcinoma Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.PMC10918499Galanti DBordonaro SRossi EFilippi RPalesandro ERoviello GLa Russa FDoni LRossi LFare EDe Lisa MPicciotto MDe Lisi DDel Re MTesti IBassanelli MGentile ALIerino DVittimberga IDalla Volta APiscazzi ABortolus RCaruso DAttademo LPasqualini AFarolfi AMaffezzoli MBuffoni MLo Vecchio MPignata SFontana AVeccia ARussi EGBruni AGuarneri ASPepe ASoraru MMigliaccio FFanelli MPitre ADi Costanzo FDi Lorenzo GGuglielmo PMalgeri ASanguedolce FVerde AMurianni VRizzo AMorelli FZonno ABarra SNasso CNaglieri EHernandez FMUrso LGualtieri SIaia MLPantano FSecondino SBaier SPelin GMSantoni MBasile DRollo LSirotova ZBidin LMaiello EArtemi ALombardo LFilograna AMosca ADi Maio MCicero GLLatteri FPrati VDepetris ILipari HMCocorocchio EAtzori FStellato MGamba TLenci EClaps MCapacci SRossi VBuonerba CVignani FBaldazzi VMennitto APaccagnella ERecine FTortora VBuonerba LRizzo MCecchi LGCordua NRoberto MToma ICasadei COrtega CBearz AChiuri VEGambale EMaiorano BAMencoboni MPilato BAieta MDi Francesco SFebbraro AMurgia VIncorvaia LCavasin NZumstein LAlberti MLandriscina MDi Tullio PGhilardi LSalesi NLlaja Obispo MAZanardi EChiari RGiannatempo PAurilio GAstore SSalfi AFormisano LZucali PAScattolin DBergamini MCinausero MRazzini GPompella LSava TCaponnetto SRInzerilli NVerzoni ELai ESbrana AGuadalupi VIngenito CScala SGridelli CErmacora PBolzacchini EGernone AAccettura CBersanelli MCattrini CPoeta MLSansi CCossu Rocca MPappagallo MNBanna GLBoccardo FTriolo RPisano CBianchi EBrighi NGrillone FRicotta RTommasi SHamzaj AMoroso SPiancastelli ASantamaria FMontanari DSartragno CGiorgione RTortorella ABasso UCecere SCFratino LEvangelista LAliprandi MZeppellini AMattana APellino AProcopio GTambaro RCarrozza FBarile CMaruzzo MConteduca VPireddu AValsecchi AAMigliari MMasini CRebuzzi SELanfranchi FCarella CBozza GDamassi ABertoni MCiccarelli SDonati DMeetURO GroupSartori DCremante MDi Civita MAAzzariti APassarelli ABauckneht MButi STamberi STucci MAltavilla ADi Napoli MVela CLancia FFoderaro STomasino MGiunta EFPoti GDri ADinota ASepe PMastrorosa AMorelli AMCapitanio UMurru MFranzese CMacerelli MBottiglieri AGasparro DPalazzo AToscani IDi Rocco RPierantoni FPiras MMercinelli CBonomi LNicodemo MPerna MPisino MDoronzo ACursano MCBenedetti BVentriglia JJubran SAntonuzzo LBronte EFrancini ELa Camera AGarattini SKBosso DUrban SBimbatti DButtigliero CSchettino CVitale MGPaolieri FCadau JDaniele BPuglia LFilaci GLuciani ABarraco CZara DMontagna BPerrone FCatalano FKinspergher SSantini DCalabro FPedrazzoli PCatalano MCoppola EGermano DSchepisi GScandurra GSerra RChiellino SGianotti EGalli LBonato ASoto Parra HRosti GBorghesi MPecoraro GPisconti SRMuto ANole FBerardi RCeresoli GLCourthod GDe Giorgi UFFederico PFornarini GTralongo PBleve SRescigno PCarteni GPacelli RSilvestro GPassalacqua RZacchi FBiasini CBruno MDi Girolamo SStumbo LD'Ostilio NDebonis SAPersano MBortot LCalvani NBaciarello GFedele PPappalardo LMaines FZago GScagliarini SCullura DCarlini PDe Summa SDe Vivo RZagonel VCampobasso DSpinelli GPArundine DMessina MPerrino MPerrucci BRibera DGianni CLombardo VNMassi DRossetti SFarnesi ACerbone LSammarco ETagliaferri PCitarella FCaffo OGiudice GCBregni MDionese MMarinelli DMessina CMucciarini CGaribaldi ESignori ACavo ASchinzari GBellia SROrlando VfalseSignificance of PD-L1 in Metastatic Urothelial Carcinoma Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.<h4>Importance</h4>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.<h4>Objectives</h4>To evaluate the association of PD-L1 with response rate and overall survival among patients with mUC treated with ICIs.<h4>Data sources</h4>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.<h4>Study selection</h4>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.<h4>Data extraction and synthesis</h4>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.<h4>Main outcomes and measures</h4>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.<h4>Results</h4>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.<h4>Conclusions and relevance</h4>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.2024-01-01T00:00:00Z2024 Mar2026-06-29T03:16:08.342Z2025-04-04T12:35:17.276ZS-EPMC109184993844647910.1001/jamanetworkopen.2024.1215