2024
1704P Potential surrogate endpoints for overall survival (OS) in immunotherapy (IO)-treated metastatic renal cell carcinoma (mRCC): An International Metastatic Database Consortium (IMDC) study
Saliby R, Xie W, Wells J, Saad E, Eid M, Semaan K, Labaki C, Ferrier E, Zarba M, Ebrahimi H, Rodriguez C, Ruiz J, Powles T, Wood L, De Velasco Oria G, Takemura K, Braun D, Heng D, Choueiri T. 1704P Potential surrogate endpoints for overall survival (OS) in immunotherapy (IO)-treated metastatic renal cell carcinoma (mRCC): An International Metastatic Database Consortium (IMDC) study. Annals Of Oncology 2024, 35: s1021-s1022. DOI: 10.1016/j.annonc.2024.08.1797.Peer-Reviewed Original ResearchFirst-line Systemic Therapy Following Adjuvant Immunotherapy in Renal Cell Carcinoma: An International Multicenter Study
El Zarif T, Semaan K, Xie W, Eid M, Zarba M, Issa W, Zhang T, Nguyen C, Alva A, Fahey C, Beckermann K, Karam J, Campbell M, Procopio G, Stellato M, Buti S, Zemankova A, Melichar B, Massari F, Mollica V, Venugopal B, Ebrahimi H, de Velasco G, Gurney H, De Giorgi U, Parikh O, Winquist E, Master V, Garcia A, Cutuli H, Ferguson T, Gross-Goupil M, Baca S, Pal S, Braun D, McKay R, Heng D, Choueiri T. First-line Systemic Therapy Following Adjuvant Immunotherapy in Renal Cell Carcinoma: An International Multicenter Study. European Urology 2024 PMID: 39147674, DOI: 10.1016/j.eururo.2024.07.016.Peer-Reviewed Original ResearchRenal cell carcinomaProgression-free survivalInternational Metastatic RCC Database ConsortiumRecurrent renal cell carcinomaTreatment-related adverse eventsSystemic therapyAdjuvant pembrolizumabOverall survivalCell carcinomaClinical outcomesIO therapyAdjuvant immunotherapyAdverse eventsVascular endothelial growth factor-targeted therapyDetect occult metastatic diseaseOutcomes of first-lineFirst-line systemic therapyFavorable-risk diseaseIO-based regimensOccult metastatic diseaseMedian follow-upKaplan-Meier methodShort follow-up periodFollow-up periodInternational multicenter study20 Evaluating intermediate endpoints for overall survival in metastatic renal cell carcinoma treated with immune checkpoint inhibitors: an IMDC study
Saliby R, Xie W, Wells C, Saad E, Eid M, Semaan K, Labaki C, Ferrier E, Zarba M, Ebrahimi H, Ravi P, Suarez C, Morales J, McKay R, Powles T, Wood L, Lalani A, Pal S, de Velasco G, Takemura K, Agarwal N, Braun D, Heng D, Choueiri T. 20 Evaluating intermediate endpoints for overall survival in metastatic renal cell carcinoma treated with immune checkpoint inhibitors: an IMDC study. The Oncologist 2024, 29: s8-s9. PMCID: PMC11301915, DOI: 10.1093/oncolo/oyae181.013.Peer-Reviewed Original ResearchTime to next therapyInternational mRCC Database ConsortiumTime to treatment failureInternational mRCC Database Consortium risk groupOverall survivalObjective responseFollow-upIndividual patient dataLandmark analysisTreatment failureInternational Metastatic Renal-Cell Carcinoma Database ConsortiumMetastatic renal cell carcinoma treated with immune checkpoint inhibitorsRisk groupsEndpoint of overall survivalMonths of follow-upIntermediate endpointsICI-based regimensImmune checkpoint inhibitorsImmune-checkpoint inhibitorsMedian follow-upAnalysis of OSAssociated with OSAssociation of OSPost-therapy initiationFollow-up time46 Radiological tumor burden is an independent risk factor for survival in patients with metastatic clear cell renal cell carcinoma (mccRCC) treated with first line immunotherapy (IO)-based regimens
Nawfal R, Eid M, Semaan K, Paul M, Saliby R, Chehade R, Machaalani M, Phillips N, Canniff J, Saad E, Vasseur D, Zarif T, Yekeduz E, Sun M, Baca S, Braun D, Xie W, Krajewski K, Choueiri T. 46 Radiological tumor burden is an independent risk factor for survival in patients with metastatic clear cell renal cell carcinoma (mccRCC) treated with first line immunotherapy (IO)-based regimens. The Oncologist 2024, 29: s25-s26. PMCID: PMC11301862, DOI: 10.1093/oncolo/oyae181.041.Peer-Reviewed Original ResearchIO-based regimensTumor burdenOverall survivalTreatment failureMultivariate analysisPrognostic factorsCT scanMetastatic clear cell renal cell carcinomaAssociated with treatment failureMultivariate Cox regression modelClear cell renal cell carcinomaHistory of nephrectomyIMDC risk groupsImmunotherapy-based regimensAssociated with OSMedian follow-upCell renal cell carcinomaDana-Farber Cancer InstituteLog-rank testIndependent risk factorRenal cell carcinomaKaplan-Meier curvesCT scan reportsManagement of patientsCox regression models22 Association of a germline single nucleotide polymorphism (SNP) in the interleukin-7 (IL7) gene with immune-related adverse events (irAEs)
Saad E, Mehrabad E, Labaki C, Saliby R, Semaan K, Eid M, Machaalani M, Chehade R, Nawfal R, Sun M, Sharon E, Shah P, Vemula S, Gupta S, Braun D, Van Allen E, Gusev A, Choueiri T. 22 Association of a germline single nucleotide polymorphism (SNP) in the interleukin-7 (IL7) gene with immune-related adverse events (irAEs). The Oncologist 2024, 29: s1-s2. PMCID: PMC11301885, DOI: 10.1093/oncolo/oyae181.003.Peer-Reviewed Original ResearchImmune-related adverse eventsMetastatic non-small cell lung cancerMetastatic renal cell carcinomaImmune checkpoint inhibitorsProgression-free survivalWhole-exome sequencingRecurrent grade 2Overall survivalGrade 2Interleukin-7Single nucleotide polymorphismsNivolumab armPembrolizumab armSomatic alterationsAdverse eventsTreatment armsPrediction of immune-related adverse eventsCumulative rates of adverse eventsTumor whole-exome sequencingRates of grade 2Non-small cell lung cancerGermline single nucleotide polymorphismsClinical trials of patientsAssociated with significantly higher ratesPD-1 inhibitors24 Applying genomic analysis to refine unclassified renal cell carcinoma
Yekeduz E, Braun D, Chehade R, Eid M, Labaki C, Machaalani M, Nassar A, Nawfal R, Saad E, Saliby R, Semaan K, Sun M, Hirsch M, Ürün Y, Zarif T, Choueiri T. 24 Applying genomic analysis to refine unclassified renal cell carcinoma. The Oncologist 2024, 29: s20-s20. PMCID: PMC11301928, DOI: 10.1093/oncolo/oyae181.032.Peer-Reviewed Original ResearchRenal cell carcinomaClear cell RCCRenal cell carcinoma subtypesAmerican Association for Cancer ResearchPapillary RCCGenomic alterationsOverall survivalNF2 alterationsCell carcinomaGenomic profilingPapillary renal cell carcinomaSubtype of renal cell carcinomaChromophobe renal cell carcinomaProportion of female patientsClear cell renal cell carcinomaMedian overall survivalCell renal cell carcinomaFrequent genomic alterationsCo-mutated genesCompare categorical variablesBenjamini-Hochberg correctionOncogenic signaling pathwaysMetastatic sitesFrequent subtype of renal cell carcinomaPrimary tumorCharacterizing genomic alterations in patients with metastatic urothelial carcinoma (mUC) treated with enfortumab-vedotin (EV) with a focus on 1q23.3.
Saliby R, Semaan K, Epstein I, Liria S, Dall C, Saad E, Eid M, Canniff J, Kwak L, Berg S, Mantia C, McGregor B, Braun D, CHOUEIRI T, Bellmunt J. Characterizing genomic alterations in patients with metastatic urothelial carcinoma (mUC) treated with enfortumab-vedotin (EV) with a focus on 1q23.3. Journal Of Clinical Oncology 2024, 42: e16570-e16570. DOI: 10.1200/jco.2024.42.16_suppl.e16570.Peer-Reviewed Original ResearchMetastatic urothelial carcinomaToxicity-free survivalProgression-free survivalEnfortumab vedotinOverall survivalProgressive diseaseTwo-copy deletionGenomic alterationsClinical outcomesAssociation of genomic alterationsNumerically longer OSDana-Farber Cancer InstituteLog-rank testFisher's exact testUnivariate Cox regressionAdvanced UCLonger OSUrothelial carcinomaSomatic alterationsDana-FarberExact testCox regressionEV efficacyPatientsImprove outcomesApplying genomic analysis to refine unclassified renal cell carcinoma.
Yekeduz E, Braun D, El Hajj Chehade R, Eid M, Labaki C, Machaalani M, Nassar A, Nawfal R, Saad E, Saliby R, Semaan K, Sun M, Hirsch M, Ürün Y, El Zarif T, CHOUEIRI T. Applying genomic analysis to refine unclassified renal cell carcinoma. Journal Of Clinical Oncology 2024, 42: 4551-4551. DOI: 10.1200/jco.2024.42.16_suppl.4551.Peer-Reviewed Original ResearchRenal cell carcinomaClear cell RCCRenal cell carcinoma subtypesAmerican Association for Cancer ResearchPapillary RCCGenomic alterationsOverall survivalCell carcinomaGenomic profilingPapillary renal cell carcinomaSubtype of renal cell carcinomaChromophobe renal cell carcinomaProportion of female patientsClear cell renal cell carcinomaMedian overall survivalCell renal cell carcinomaCo-mutated genesCompare categorical variablesBenjamini-Hochberg correctionOncogenic signaling pathwaysMetastatic sitesFrequent subtype of renal cell carcinomaPrimary tumorChi-square testNF2 alterationsMolecular analysis of the HCRN GU16-260-Cohort A phase II study of first-line (1L) nivolumab (nivo) and salvage nivo + ipilimumab (ipi) in patients (pts) with advanced clear cell renal cell carcinoma (accRCC).
Zaemes J, Hugaboom M, Shah V, Haas N, McDermott D, Jegede O, Bilen M, Stein M, Sosman J, Alter R, Plimack E, Hurwitz M, Wu C, Einstein D, Hammers H, Signoretti S, West D, Denize T, Atkins M, Braun D. Molecular analysis of the HCRN GU16-260-Cohort A phase II study of first-line (1L) nivolumab (nivo) and salvage nivo + ipilimumab (ipi) in patients (pts) with advanced clear cell renal cell carcinoma (accRCC). Journal Of Clinical Oncology 2024, 42: 4546-4546. DOI: 10.1200/jco.2024.42.16_suppl.4546.Peer-Reviewed Original ResearchObjective response rateImmune checkpoint blockadeProgression-free survivalProgressive diseaseAnti-VEGFOverall survivalAssociated with higher progression-free survivalTumor samplesAdvanced clear cell renal cell carcinomaCombined immune checkpoint blockadeHigher progression-free survivalIncreased PFSImmune checkpoint blockade therapyShorter progression-free survivalClear cell renal cell carcinomaAnti-VEGF therapyCell renal cell carcinomaWeeks of therapyRenal cell carcinomaBiomarkers of efficacyFFPE tumor samplesNIVO monotherapyCheckpoint blockadeDecreased OSProspective trialsEvaluating intermediate endpoints (IE) for overall survival (OS) in metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICI): An IMDC study.
Saliby R, Xie W, Wells J, Saad E, Eid M, Labaki C, Semaan K, Ferrier E, Lemelin A, Suárez C, Ruiz-Morales J, Powles T, Wood L, Ebrahimi H, de Velasco G, Takemura K, Agarwal N, Braun D, Heng D, Choueiri T. Evaluating intermediate endpoints (IE) for overall survival (OS) in metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICI): An IMDC study. Journal Of Clinical Oncology 2024, 42: 400-400. DOI: 10.1200/jco.2024.42.4_suppl.400.Peer-Reviewed Original ResearchTime to next therapyTime to treatment failureInternational mRCC Database ConsortiumImmune checkpoint inhibitorsMetastatic renal cell carcinomaOverall survivalIntermediate endpointsHazard ratioInternational mRCC Database Consortium risk groupTreated with immune checkpoint inhibitorsDual immune checkpoint inhibitorsICI startICI-based regimensAssociated with OSAssociation of OSEndpoint of OSRenal cell carcinomaCheckpoint inhibitorsNext therapyMetastatic sitesDrug cessationTreatment failurePrimary endpointCell carcinomaMedian agePD-1 Expression on Intratumoral Regulatory T Cells Is Associated with Lack of Benefit from Anti-PD-1 Therapy in Metastatic Clear-Cell Renal Cell Carcinoma Patients.
Denize T, Jegede O, Matar S, El Ahmar N, West D, Walton E, Bagheri A, Savla V, Nabil Laimon Y, Gupta S, Vemula S, Braun D, Burke K, Catalano P, Freeman G, Motzer R, Atkins M, McDermott D, Sharpe A, Choueiri T, Signoretti S. PD-1 Expression on Intratumoral Regulatory T Cells Is Associated with Lack of Benefit from Anti-PD-1 Therapy in Metastatic Clear-Cell Renal Cell Carcinoma Patients. Clinical Cancer Research 2024, 30: 803-813. PMID: 38060202, PMCID: PMC10922154, DOI: 10.1158/1078-0432.ccr-23-2274.Peer-Reviewed Original ResearchPD-1 expressionObjective response rateProgression-free survivalLow objective response rateShorter progression-free survivalPD-1 blockadeRegulatory T cellsShorter overall survivalOverall survivalPD-1Nivolumab armT cellsMetastatic clear-cell renal cell carcinoma patientsMetastatic clear cell renal cell carcinomaAnti-PD-1 therapyIntratumoral regulatory T cellsClear cell renal cell carcinoma patientsRenal cell carcinoma patientsClear cell renal cell carcinomaPD-1 inhibitorsPD-1 inhibitionCell carcinoma patientsCell renal cell carcinomaExpression of CD8Tumor-infiltrating TregsUpdate on Biomarkers in Renal Cell Carcinoma.
Saliby R, Saad E, Kashima S, Schoenfeld D, Braun D. Update on Biomarkers in Renal Cell Carcinoma. American Society Of Clinical Oncology Educational Book 2024, 44: e430734. PMID: 38207251, DOI: 10.1200/edbk_430734.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsRenal cell carcinomaCell carcinomaMetastatic renal cell carcinomaTumor intrinsic featuresImmune checkpoint inhibitorsRobust predictive biomarkersCheckpoint inhibitorsDurable responsesOverall survivalCare regimensPathological characteristicsPredictive biomarkersTherapeutic responseTreatment paradigmImmune systemHost factorsTranscriptional signatureGenomic alterationsTumor heterogeneityBiomarkersCarcinomaBiomarker discoveryInnovative technological approachesRegimens
2023
A Pooled Analysis of 3 Phase II Trials of Salvage Nivolumab/Ipilimumab After Nivolumab in Renal Cell Carcinoma
McKay R, Leucht K, Xie W, Jegede O, Braun D, Atkins M, Grimm M, Choueiri T. A Pooled Analysis of 3 Phase II Trials of Salvage Nivolumab/Ipilimumab After Nivolumab in Renal Cell Carcinoma. The Oncologist 2023, 29: 324-331. PMID: 37950901, PMCID: PMC10994246, DOI: 10.1093/oncolo/oyad298.Peer-Reviewed Original ResearchObjective response rateClear cell renal cell carcinomaRenal cell carcinomaProgression-free survivalCell renal cell carcinomaAdvanced clear cell renal cell carcinomaOverall survivalCell carcinomaPooled analysisSix-month progression-free survivalBest objective response rateActivity of nivolumabInitiation of nivolumabNivolumab/ipilimumabPoor-risk diseasePhase II trialEligible patientsII trialObjective responsePrior immunotherapyImproved survivalRisk diseaseClinical trialsIpilimumabNivolumabCirculating and Intratumoral Immune Determinants of Response to Atezolizumab plus Bevacizumab in Patients with Variant Histology or Sarcomatoid Renal Cell Carcinoma
Saliby R, Zarif T, Bakouny Z, Shah V, Xie W, Flippot R, Denize T, Kane M, Madsen K, Ficial M, Hirsch L, Wei X, Steinharter J, Harshman L, Vaishampayan U, Severgnini M, McDermott D, Lee G, Xu W, Van Allen E, McGregor B, Signoretti S, Choueiri T, McKay R, Braun D. Circulating and Intratumoral Immune Determinants of Response to Atezolizumab plus Bevacizumab in Patients with Variant Histology or Sarcomatoid Renal Cell Carcinoma. Cancer Immunology Research 2023, 11: 1114-1124. PMID: 37279009, PMCID: PMC10526700, DOI: 10.1158/2326-6066.cir-22-0996.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaT cellsWorse PFSImmunotherapy responseCell carcinomaPeripheral immune cell populationsWorse progression-free survivalSarcomatoid renal cell carcinomaPhase II clinical trialImmunotherapy-based combinationsValue of tumourPoor-risk patientsProgression-free survivalImmune cell populationsVascular endothelial growth factorKidney cancer diagnosisEndothelial growth factorFuture biomarker studiesLack of responseInflammatory modulesExhausted CD8Variant histologyOverall survivalPD-L1Sarcomatoid differentiation
2022
Dual CDKN2A/MTAP loss compared to CDKN2A loss alone and response to immune-checkpoint inhibitors (ICI) in advanced solid tumors.
Adib E, Nassar A, El Zarif T, Kale N, Rakaee M, Mouhieddine T, Abou Alaiwi S, Freeman D, Labban M, Akl E, Haddad R, Hodi F, Sonpavde G, Giannakis M, Braun D, Gusev A, Choueiri T, Overstreet E, Stone E, Kwiatkowski D. Dual CDKN2A/MTAP loss compared to CDKN2A loss alone and response to immune-checkpoint inhibitors (ICI) in advanced solid tumors. Journal Of Clinical Oncology 2022, 40: 2622-2622. DOI: 10.1200/jco.2022.40.16_suppl.2622.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsTumor-infiltrating lymphocytesLow TIL densityTreatment failureOverall survivalHazard ratioTIL densityGenomic alterationsCell carcinomaNon-small cell lung cancerDana-Farber Cancer InstituteCancer typesNeck squamous cell carcinomaAdvanced solid tumorsConcurrent systemic therapyCell lung cancerSquamous cell carcinomaTumor mutational burdenRenal cell carcinomaMelanoma tissue samplesMTAP lossHomozygous deletionECOG PSEsophagogastric carcinomaMetastatic setting