2024
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
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 modelsExpression of the receptor tyrosine kinase AXL and clinical outcomes to cabozantinib and everolimus in patients with metastatic renal cell carcinoma enrolled in the METEOR trial.
Nabil Laimon Y, Paul M, Ghandour F, El Ahmar N, Matar S, Denize T, Bagheri Sheshdeh A, Savla V, Mohanna R, Sun M, Saliby R, Saad E, Machaalani M, Braun D, Aftab D, Xie W, CHOUEIRI T, Signoretti S. Expression of the receptor tyrosine kinase AXL and clinical outcomes to cabozantinib and everolimus in patients with metastatic renal cell carcinoma enrolled in the METEOR trial. Journal Of Clinical Oncology 2024, 42: 4543-4543. DOI: 10.1200/jco.2024.42.16_suppl.4543.Peer-Reviewed Original ResearchProgression-free survivalAssociated with progression-free survivalReceptor tyrosine kinase AXLTyrosine kinase inhibitorsRenal cell carcinomaImmune cellsMETEOR trialTyrosine kinase AXLAxl expressionTumor cellsCell carcinomaAssociated with shorter progression-free survivalMetastatic clear cell renal cell carcinomaAnti-PD-1 therapyLevels of AXL expressionMetastatic renal cell carcinomaMultitargeted tyrosine kinase inhibitorPresence of bone metastasesShorter progression-free survivalClear cell renal cell carcinomaIMDC risk groupsPretreatment tumor tissueVEGFR-TKI treatmentCell renal cell carcinomaDouble immunohistochemistry stainingAdvanced renal cell cancer combination immunotherapy clinical trial (ARCITECT; HCRN GU 22-587).
Serzan M, Jegede O, Alter R, Bilen M, Braun D, Einstein D, Haas N, Herchenhorn D, King J, Runcie K, Sosman J, Sternberg C, Yang Y, Signoretti S, CHOUEIRI T, Atkins M. Advanced renal cell cancer combination immunotherapy clinical trial (ARCITECT; HCRN GU 22-587). Journal Of Clinical Oncology 2024, 42: tps4614-tps4614. DOI: 10.1200/jco.2024.42.16_suppl.tps4614.Peer-Reviewed Original ResearchTyrosine kinase inhibitorsArm BArm APrimary endpointRate of immune-related adverse eventsMetastatic clear cell renal cell carcinomaImmune-related adverse eventsMolecular predictors of responseVEGF receptor tyrosine kinase inhibitorReceptor tyrosine kinase inhibitorsEnhance T cell primingOne-sided significance levelClear cell renal cell carcinomaAnti-PD1 inhibitorsIMDC risk groupsTreatment free intervalProgression-free survivalT cell primingTreatment-free survivalCell renal cell carcinomaSubpopulations of TregsFirst-line treatmentRenal cell carcinomaPredictors of responseAssociated with increased presenceIntratumoral T-cell infiltration and response to nivolumab plus ipilimumab in patients with metastatic clear cell renal cell carcinoma from the CheckMate-214 trial.
Matar S, Jegede O, Denize T, Ghandour F, Nabil Laimon Y, El Ahmar N, Bagheri Sheshdeh A, Savla V, Mohanna R, Catalano P, Braun D, Sun M, Gupta S, Vemula S, Freeman G, Motzer R, Atkins M, McDermott D, CHOUEIRI T, Signoretti S. Intratumoral T-cell infiltration and response to nivolumab plus ipilimumab in patients with metastatic clear cell renal cell carcinoma from the CheckMate-214 trial. Journal Of Clinical Oncology 2024, 42: 4536-4536. DOI: 10.1200/jco.2024.42.16_suppl.4536.Peer-Reviewed Original ResearchProgression-free survivalAssociated with progression-free survivalMultiplex immunofluorescenceClinical trialsClinical outcomesMetastatic clear cell renal cell carcinomaIntratumoral T cell infiltrationTreated with nivolumab monotherapyMetastatic clear cell RCCClear cell renal cell carcinomaResponse to nivolumabT cell infiltrationCell renal cell carcinomaPoor-risk patientsRenal cell carcinomaClear cell RCCFormalin fixed paraffinContinuous variablesNivolumab monotherapyCox proportional hazardsAntigen-experiencedCell RCCCell carcinomaLogistic regression modelsPositive associationAdvanced renal cell cancer combination immunotherapy clinical trial (ARCITECT; HCRN GU 22-587).
Serzan M, Jegede O, Bilen M, Braun D, Einstein D, Haas N, Hammers H, King J, Runcie K, Sosman J, Sternberg C, Yang Y, Choueiri T, Signoretti S, Atkins M. Advanced renal cell cancer combination immunotherapy clinical trial (ARCITECT; HCRN GU 22-587). Journal Of Clinical Oncology 2024, 42: tps492-tps492. DOI: 10.1200/jco.2024.42.4_suppl.tps492.Peer-Reviewed Original ResearchTyrosine kinase inhibitorsArm BArm APrimary endpointRate of immune-related adverse eventsMetastatic clear cell renal cell carcinomaImmune-related adverse eventsMolecular predictors of responseVEGF receptor tyrosine kinase inhibitorReceptor tyrosine kinase inhibitorsEnhance T cell primingOne-sided significance levelClear cell renal cell carcinomaAnti-PD1 inhibitorsIMDC risk groupsTreatment free intervalProgression-free survivalT cell primingTreatment-free survivalCell renal cell carcinomaSubpopulations of TregsFirst-line treatmentRenal cell carcinomaPredictors of responseAnti-tumor activityPD-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 Tregs
2023
Emerging Biomarkers of Response to Systemic Therapies in Metastatic Clear Cell Renal Cell Carcinoma
Labaki C, Saliby R, Bakouny Z, Saad E, Semaan K, Eid M, Lalani A, Choueiri T, Braun D. Emerging Biomarkers of Response to Systemic Therapies in Metastatic Clear Cell Renal Cell Carcinoma. Hematology/Oncology Clinics Of North America 2023, 37: 937-942. PMID: 37407357, DOI: 10.1016/j.hoc.2023.05.021.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMetastatic clear cell renal cell carcinomaClear cell renal cell carcinomaCell renal cell carcinomaRenal cell carcinomaSystemic therapyCell carcinomaImmunotherapy-based regimensBiomarkers of responseSystemic regimensClinical responseValid biomarkersPromising biomarkerHeterogeneous outcomesTherapyBiomarkersRegimensPatientsCarcinomaMccRCCResponse
2022
Transcriptomic Correlates of Tumor Cell PD-L1 Expression and Response to Nivolumab Monotherapy in Metastatic Clear Cell Renal Cell Carcinoma.
Denize T, Hou Y, Pignon J, Walton E, West D, Freeman G, Braun D, Wu C, Gupta S, Motzer R, Atkins M, McDermott D, Choueiri T, Shukla S, Signoretti S. Transcriptomic Correlates of Tumor Cell PD-L1 Expression and Response to Nivolumab Monotherapy in Metastatic Clear Cell Renal Cell Carcinoma. Clinical Cancer Research 2022, 28: 4045-4055. PMID: 35802667, PMCID: PMC9481706, DOI: 10.1158/1078-0432.ccr-22-0923.Peer-Reviewed Original ResearchConceptsTC PD-L1 expressionClear cell renal cell carcinomaPD-L1 expressionMetastatic clear cell renal cell carcinomaCell renal cell carcinomaRenal cell carcinomaProliferation-related pathwaysCell proliferation-related pathwaysClinical outcomesTumor cellsCell carcinomaTumor cell PD-L1 expressionAnti-PD-1 monotherapyPD-L1 positive tumorsHigher objective response rateLonger progression-free survivalTumor-infiltrating immune cellsTC PD-L1Objective response ratePD-L1 statusProgression-free survivalT-cell activation signaturesCheckMate 025 trialNivolumab monotherapyPD-L1