2024
Cabozantinib and nivolumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial
Ebrahimi H, Dizman N, Meza L, Malhotra J, Li X, Dorff T, Frankel P, Llamas-Quitiquit M, Hsu J, Zengin Z, Alcantara M, Castro D, Mercier B, Chawla N, Chehrazi-Raffle A, Barragan-Carrillo R, Jaime-Casas S, Govindarajan A, Gillece J, Trent J, Lee P, Parks T, Takahashi M, Hayashi A, Kortylewski M, Caporaso J, Lee K, Tripathi A, Pal S. Cabozantinib and nivolumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial. Nature Medicine 2024, 1-10. PMID: 38942995, DOI: 10.1038/s41591-024-03086-4.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaProgression-free survivalRenal cell carcinomaCell carcinomaToxicity profileAbundance of Bifidobacterium sppControl armTreatment-naive participantsFirst-line treatmentPhase 1 studyPhase 1 trialSarcomatoid componentOpen-labelHistological confirmationPrimary endpointSecondary endpointsNo significant differenceClear cellNivolumabInvestigator-initiatedClinical outcomesCabozantinibClinical activityStool samplesStudy armsRenal Cell Carcinoma of Variant Histology: New Biologic Understanding Leads to Therapeutic Advances.
Salgia N, Zengin Z, Pal S, Dizman N. Renal Cell Carcinoma of Variant Histology: New Biologic Understanding Leads to Therapeutic Advances. American Society Of Clinical Oncology Educational Book 2024, 44: e438642. PMID: 38776514, PMCID: PMC11235416, DOI: 10.1200/edbk_438642.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaPapillary renal cell carcinomaBiology of renal cell carcinomaHistology renal cell carcinomaPatient populationRenal cell carcinoma histologyMetastatic renal cell carcinomaRenal cell carcinoma casesOptimization of treatment regimensNon-clear cellPrecision oncology approachesDiagnosed solid tumorsSarcomatoid dedifferentiationVariant histologyRare subtypeHistopathological subtypesCell carcinomaSolid tumorsClinical featuresTreatment regimensClinical findingsOncology approachesTherapeutic advancesTherapeutic approachesUnique pathogenesesImpact of CBM588 on gut microbiome composition and dysbiosis in patients receiving frontline immune checkpoint inhibitor (ICI) combinations for metastatic renal cell carcinoma (mRCC).
Dizman N, Ebrahimi H, Barragán Carrillo R, Meza L, Bergerot P, Dorff T, Hsu J, Zengin Z, Castro D, Chehrazi-Raffle A, Tripathi A, Trent J, Takahashi M, Oka K, Higashi S, Caporaso G, Lee K, Pal S. Impact of CBM588 on gut microbiome composition and dysbiosis in patients receiving frontline immune checkpoint inhibitor (ICI) combinations for metastatic renal cell carcinoma (mRCC). Journal Of Clinical Oncology 2024, 42: 4550-4550. DOI: 10.1200/jco.2024.42.16_suppl.4550.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaImmune checkpoint inhibitorsStandard of careStandard of care cohortGut microbiome compositionMicrobiome compositionClinical outcomesCell metastatic renal cell carcinomaRandomized phase I clinical trialGut dysbiosisAssociated with ICI responseStandard of care regimensClinically relevant microbial speciesCompared gut microbiome diversityPhase I clinical trialClinically relevant speciesPhase III studyRelevant microbial speciesBaseline to weekFirst-line treatmentGut microbiome diversityRatio of Firmicutes/BacteroidetesRenal cell carcinomaWilcoxon matched pairs testAnalyzed stool samplesImpact of Latino ethnicity on the gut microbiome composition of patients with metastatic renal cell cancer (mRCC).
Barragán Carrillo R, Dizman N, Ebrahimi H, Meza L, Bergerot P, Dorff T, Hsu J, Zengin Z, Salgia N, Chehrazi-Raffle A, Tripathi A, Castro D, Mercier B, Caporaso G, Lee K, Pal S. Impact of Latino ethnicity on the gut microbiome composition of patients with metastatic renal cell cancer (mRCC). Journal Of Clinical Oncology 2024, 42: 4521-4521. DOI: 10.1200/jco.2024.42.16_suppl.4521.Peer-Reviewed Original ResearchMetastatic renal cell cancerImmune checkpoint inhibitionGut microbiome compositionBeta diversityBacterial speciesANCOM-BCAbundance of bacterial speciesWhole metagenome sequencingF/B ratioRatio of Firmicutes/BacteroidetesStool specimensShannon diversity indexR. inulinivoransE. rectaleRenal cell cancerTaxonomic profilesMetagenomic sequencingAlpha diversityGut microbiotaGut microbiomeMicrobiome compositionBray-CurtisDiversity indexComposition of patientsGut dysbiosisPrevalence of Dietary Modification and Supplement Use in Patients with Metastatic Renal Cell Carcinoma Receiving Systemic Therapy
Ebrahimi H, Battle D, Salgia N, Zengin Z, Dizman N, Meza L, Bergerot C, Barragan-Carrillo R, Hsu J, Castro D, Mercier B, Chawla N, Li X, Tripathi A, Liu S, Chehrazi-Raffle A, Vaishampayan U, Staehler M, Pal S. Prevalence of Dietary Modification and Supplement Use in Patients with Metastatic Renal Cell Carcinoma Receiving Systemic Therapy. Nutrients 2024, 16: 1630. PMID: 38892563, PMCID: PMC11174627, DOI: 10.3390/nu16111630.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaRenal cell carcinomaCell carcinomaDietary modificationSupplement useDiagnosis of renal cell carcinomaFirst-line treatmentSupplement usageSystemic therapyCombination therapyAntineoplastic therapyKetogenic dietCarcinomaCancer therapyMediterranean dietPhysician-patient dialoguePatientsTherapyCancer treatmentGrowing body of evidenceBody of evidenceDietary changesCancerCancer diagnosisCannabidiolCRE24-052: Hyperfibrinolysis as the Primary Presenting Sign of Metastatic Prostate Cancer: A Diagnostic Challenge
Lobo A, Zengin Z, Kenworthy C, Sharda A. CRE24-052: Hyperfibrinolysis as the Primary Presenting Sign of Metastatic Prostate Cancer: A Diagnostic Challenge. Journal Of The National Comprehensive Cancer Network 2024, 22 DOI: 10.6004/jnccn.2023.7326.Peer-Reviewed Original ResearchImpact of Synchronous versus Metachronous Metastasis on Outcomes in Patients with Metastatic Renal Cell Carcinoma Treated with First-line Immune Checkpoint Inhibitor–based Combinations
Gebrael G, Meza L, Li X, Zengin Z, Sayegh N, Ebrahimi H, Tripathi N, Castro D, Mercier B, Barragan-Carrillo R, Li H, Chehrazi-Raffle A, Swami U, Tripathi A, Agarwal N, Maughan B, Pal S. Impact of Synchronous versus Metachronous Metastasis on Outcomes in Patients with Metastatic Renal Cell Carcinoma Treated with First-line Immune Checkpoint Inhibitor–based Combinations. European Urology Focus 2024 PMID: 38580524, DOI: 10.1016/j.euf.2024.03.006.Peer-Reviewed Original ResearchTime to treatment failureDisease control rateRenal cell carcinomaSynchronous metastasesMetachronous metastasesOverall survivalMetachronous metastatic renal cell carcinomaMedian time to treatment failureICI-based combination therapyAssociated with worse OSMetastatic renal cell carcinomaFirst-line immunotherapyICI-based combinationsRenal cell carcinoma diagnosisDiagnosis of kidney cancerHypothesis-generating studyMedian OSMetachronous groupPoor OSTreatment failureCombination therapyMetastasis onsetCell carcinomaSurvival outcomesClinical outcomesInfigratinib Versus Placebo for Patients with High-risk Resected Urothelial Cancer Bearing an FGFR3 Genomic Alteration: Results from the PROOF302 Phase 3 Trial
Pal S, Grivas P, Gupta S, Dizman N, Zengin Z, Valderrama B, Rodriguez-Vida A, Roghmann F, Sevillano Fernandez E, Matin S, Loriot Y, Sridhar S, Sonpavde G, Fleming M, Lerner S, Bellmunt J, Master V, Tripathi A, Davis K, van Veenhuyzen D, Weng R, Daneshmand S. Infigratinib Versus Placebo for Patients with High-risk Resected Urothelial Cancer Bearing an FGFR3 Genomic Alteration: Results from the PROOF302 Phase 3 Trial. European Urology 2024 PMID: 38580518, DOI: 10.1016/j.eururo.2024.03.023.Peer-Reviewed Original ResearchBarriers to Clinical Trial Implementation Among Community Care Centers
Ebrahimi H, Megally S, Plotkin E, Shivakumar L, Salgia N, Zengin Z, Meza L, Chawla N, Castro D, Dizman N, Bhagat R, Liv S, Li X, Rock A, Liu S, Tripathi A, Dorff T, Oyer R, Boehmer L, Pal S, Chehrazi-Raffle A. Barriers to Clinical Trial Implementation Among Community Care Centers. JAMA Network Open 2024, 7: e248739. PMID: 38683608, PMCID: PMC11059033, DOI: 10.1001/jamanetworkopen.2024.8739.Peer-Reviewed Original ResearchConceptsClinical trial implementationClinical trial enrollmentTrial enrollmentUnmet needsCancer clinical trial enrollmentHealth care practicesPatients seeking careTrial implementationCommunity care centersCommunity oncology settingNational survey studyRural practiceClinical research opportunitiesCare practicesCare settingsCancer clinicOncology settingLimited staffingPractice changeRural settingsOncology clinicMain OutcomesHispanic residentsReferral practicesTrial participantsClinical implications of AR alterations in advanced prostate cancer: a multi-institutional collaboration
Zengin Z, Henderson N, Park J, Ali A, Nguyen C, Hwang C, Barata P, Bilen M, Graham L, Mo G, Kilari D, Tripathi A, Labriola M, Rothstein S, Garje R, Koshkin V, Patel V, Schweizer M, Armstrong A, McKay R, Alva A, Dorff T. Clinical implications of AR alterations in advanced prostate cancer: a multi-institutional collaboration. Prostate Cancer And Prostatic Diseases 2024, 1-7. PMID: 38383885, DOI: 10.1038/s41391-024-00805-3.Peer-Reviewed Original ResearchAndrogen receptor-targeted agentsCastration-resistant prostate cancerAR alterationsAR amplificationAR mutationsProstate cancerGene alterationsClinical outcomesAssociated with longer time to progressionCastration-resistant prostate cancer patientsGenomic testingLonger time to progressionTime to progressionAdvanced prostate cancerReceptor-targeted agentsPSA responseMetastatic diseaseOverall survivalMulti-institutional collaborative effortTestosterone suppressionMedian ageTargeted agentsProspective studyTreatment outcomesTherapeutic strategiesAssociation between thymectomy and incidence of renal cell carcinoma (RCC).
Barragan-Carrillo R, Ebrahimi H, Chawla N, Salgia N, Castro D, Chehrazi-Raffle A, Dizman N, Hsu J, Meza L, Zengin Z, LeVee A, Tripathi A, Dorff T, Bergerot C, Bergerot P, Eilber K, Dallas K, Pal S. Association between thymectomy and incidence of renal cell carcinoma (RCC). Journal Of Clinical Oncology 2024, 42: 371-371. DOI: 10.1200/jco.2024.42.4_suppl.371.Peer-Reviewed Original ResearchRenal cell carcinomaIncidence of nephrectomyIncidence of renal cell carcinomaMedian age of patientsFrequency of nephrectomyAge of patientsT cell productionProportion of patientsRate of nephrectomyFisher's exact testGeneral populationAge-matched populationICD-9/10 codesPopulation-based cohortPopulation-based studyImmunogenic cancerPrior thymectomyChi-square testCell carcinomaMedian ageSurgical interventionNephrectomyThymectomyExact testOSHPD databaseEvolution of the functionality of microbial communities in patients with metastatic renal cell carcinoma (mRCC) receiving cabozantinib (cabo)/nivolumab (nivo) with or without CBM588: A randomized clinical trial.
Ebrahimi H, Meza L, Lee K, Malhotra J, Alcantara M, Zengin Z, Dizman N, Hsu J, Llamas-Quitiquit M, Castro D, Mercier B, Barragan-Carrillo R, Chawla N, Li X, Liu S, Chehrazi-Raffle A, Dorff T, Frankel P, Tripathi A, Pal S. Evolution of the functionality of microbial communities in patients with metastatic renal cell carcinoma (mRCC) receiving cabozantinib (cabo)/nivolumab (nivo) with or without CBM588: A randomized clinical trial. Journal Of Clinical Oncology 2024, 42: 460-460. DOI: 10.1200/jco.2024.42.4_suppl.460.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaMetabolic pathwaysClinical outcomesAnnotated open reading framesFunction of microbial communitiesMetatranscriptomic sequencing dataWhole metagenome sequencingOpen reading frameGut microbial functionsGut microbiome functionsResponse rate to sorafenibExperimental armElectron transfer chainCancer cell typesAssociated with clinical outcomesRenal cell carcinomaReading frameSequence dataTaxonomic profilesBiosynthesis pathwayMetagenomic sequencingMicrobiome functionMicrobial functionsMolecular functionsRandomized clinical trialsImpact of insurance payer status (IS) on practice patterns and overall survival (OS) in patients (pts) with metastatic urothelial carcinoma (mUC).
Mercier B, Tripathi N, Govindarajan A, Gebrael G, Narang A, Li X, Castro D, Chehrazi-Raffle A, Dizman N, Ebrahimi H, Chawla N, Hsu J, Bergerot C, Barragan-Carrillo R, Zengin Z, Meza L, Pal S, Agarwal N, Tripathi A. Impact of insurance payer status (IS) on practice patterns and overall survival (OS) in patients (pts) with metastatic urothelial carcinoma (mUC). Journal Of Clinical Oncology 2024, 42: 547-547. DOI: 10.1200/jco.2024.42.4_suppl.547.Peer-Reviewed Original ResearchMetastatic urothelial carcinomaOverall survivalCox proportional hazards multivariate modelPresence of visceral metastasesChi-square test/Fisher's exact testIS groupPractice patternsPredictors of OSKaplan-Meier methodImpact practice patternsLog-rank testMedicare groupPrivate insuranceMulti-institutional studyANOVA/Kruskal-Wallis testVisceral metastasesInsurance payer statusNeoadjuvant chemotherapyNCI-designated comprehensive cancer centerSystemic therapyUrothelial carcinomaMedian ageBaseline characteristicsExact testClinical trial participationClinical and molecular characterization of urothelial (UC) vs. small cell carcinoma (SCC) of the urinary tract.
Chawla N, Mercier B, Govindarajan A, Li X, Castro D, Ebrahimi H, Barragan-Carrillo R, Zang P, LeVee A, Dizman N, Hsu J, Meza L, Zengin Z, Salgia N, Chehrazi-Raffle A, Dorff T, Pal S, Tripathi A. Clinical and molecular characterization of urothelial (UC) vs. small cell carcinoma (SCC) of the urinary tract. Journal Of Clinical Oncology 2024, 42: 682-682. DOI: 10.1200/jco.2024.42.4_suppl.682.Peer-Reviewed Original ResearchSmall cell carcinomaFeatures of small cell carcinomaGenome sequencePrevalence of genomic alterationsSmall cell carcinoma patientsSmall cell carcinoma groupFrequency of CDKN2APrevalence of TP53Fisher's exact testTumor gradeCell carcinomaPathological variablesUse of bloodUrinary tractBladder cancerExact testGenomic alterationsProportion Z testGenomic profilingGenomic featuresPathological featuresTherapeutic strategiesGenomic datasetsGenomic characteristicsBonferroni correctionCombination nivolumab and ipilimumab with and without camu camu in first-line treatment of metastatic renal cell carcinoma (mRCC).
Barragan-Carrillo R, Chawla N, Salgia N, Meza L, Zengin Z, Li X, Dizman N, Ebrahimi H, Hsu J, Castro D, Mercier B, Dorff T, Tripathi A, Bergerot C, Bergerot P, Chehrazi-Raffle A, Pal S. Combination nivolumab and ipilimumab with and without camu camu in first-line treatment of metastatic renal cell carcinoma (mRCC). Journal Of Clinical Oncology 2024, 42: tps491-tps491. DOI: 10.1200/jco.2024.42.4_suppl.tps491.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaImmune checkpoint inhibitionBaseline to weekFirst-line treatmentClinical responsePoor-risk metastatic renal cell carcinomaFirst-line treatment of metastatic renal cell carcinomaTreatment of metastatic renal cell carcinomaCombination of immune checkpoint inhibitionEfficacy of anti-PD1 therapyCombination immune checkpoint inhibitionDual immune checkpoint inhibitionCD8+ T cellsAnti-PD1 therapyImmune-related toxicitiesProgression-free survivalWeeks of therapyReduced tumor sizeTyrosine kinase inhibitorsSingle-center trialRenal cell carcinomaClear-cell RCCMouse tumor modelsOne-sided type I errorCombination nivolumabTargeting STAT3 in tumor-associated antigen-presenting cells as a strategy for kidney and bladder cancer immunotherapy
Alcantara M, Tang W, Wang D, Kaniowski D, Kang E, Dizman N, Chehrazi-Raffle A, Meza L, Zengin Z, Hall J, Hsu J, Egelston C, Moreira D, Horsager A, Pal S, Kortylewski M. Targeting STAT3 in tumor-associated antigen-presenting cells as a strategy for kidney and bladder cancer immunotherapy. Frontiers In Immunology 2024, 14: 1274781. PMID: 38259453, PMCID: PMC10800835, DOI: 10.3389/fimmu.2023.1274781.Peer-Reviewed Original ResearchImmune checkpoint blockadeDendritic cellsCancer patientsBladder cancerT cellsTumor-associated antigen-presenting cellsTherapeutic efficacyLesser extent IL-10T cell-based immunotherapyImmune checkpoint inhibitorsTumor immune evasionAntitumor immune responseCD8 T cellsRegulatory T cellsBladder cancer immunotherapyCell-based immunotherapyAntigen-presenting cellsSTAT3 activationRenal cancer patientsBladder cancer patientsImmune cell activityMyeloid immune cellsICB resistanceIpilimumab immunotherapyCheckpoint inhibitors
2023
Genomic and Transcriptomic Characteristics of Tumors of Patients with Metastatic Clear Cell Renal Cell Carcinoma Clinically Benefiting from First-Line Treatment with Ipilimumab Plus Nivolumab
Tripathi N, Meza L, Sayegh N, Govindarajan A, Byron S, Zhang J, Chigarira B, Jo Y, Zengin Z, Li H, Gebrael G, Desai A, Agarwal N, Swami U, Maughan B, Pal S. Genomic and Transcriptomic Characteristics of Tumors of Patients with Metastatic Clear Cell Renal Cell Carcinoma Clinically Benefiting from First-Line Treatment with Ipilimumab Plus Nivolumab. Kidney Cancer 2023, 7: 137-145. DOI: 10.3233/kca-230011.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaClear cell metastatic renal cell carcinomaClinical benefit groupRenal cell carcinomaClinical benefitNivolumab therapyCell carcinomaPoor-risk metastatic renal cell carcinomaMetastatic clear cell renal cell carcinomaBenefit groupClear cell renal cell carcinomaFirst-line ipilimumabIMDC risk scoresFirst-line treatmentCell renal cell carcinomaAlteration frequencyChi-square testMRCC patientsStable diseaseComplete responsePartial responseSystemic therapyLine treatmentInflammatory pathwaysTumor-specific gene expressionDifferential Impact of SPOP Mutation in Prostate and Endometrial Cancers.
Gebrael G, Zengin Z, Swami U. Differential Impact of SPOP Mutation in Prostate and Endometrial Cancers. JCO Precision Oncology 2023, 7: e2300397. PMID: 37972335, DOI: 10.1200/po.23.00397.Peer-Reviewed Original ResearchAssociation Between Time-of-Day of Immune Checkpoint Blockade Administration and Outcomes in Metastatic Renal Cell Carcinoma
Dizman N, Govindarajan A, Zengin Z, Meza L, Tripathi N, Sayegh N, Castro D, Chan E, Lee K, Prajapati S, Feng M, Loo V, Pace M, O'Brien S, Bailey E, Barragan-Carrillo R, Chehrazi-Raffle A, Hsu J, Li X, Agarwal N, Pal S. Association Between Time-of-Day of Immune Checkpoint Blockade Administration and Outcomes in Metastatic Renal Cell Carcinoma. Clinical Genitourinary Cancer 2023, 21: 530-536. PMID: 37495481, DOI: 10.1016/j.clgc.2023.06.004.Peer-Reviewed Original ResearchConceptsMetastatic renal cell carcinomaObjective response rateTreatment failureRenal cell carcinomaHazard ratioOverall survivalCell carcinomaMultivariate analysisHigh Cut-OffNivolumab/ipilimumabProspective Randomized StudyBaseline characteristicsRandomized studyClinical outcomesMedian timePreclinical evidenceUnivariate analysisPatientsResponse rateImmune systemInfusion timeStatistical significanceOutcomesCarcinomaInfusionEffect of CBM588 in combination with cabozantinib plus nivolumab for patients (pts) with metastatic renal cell carcinoma (mRCC): A randomized clinical trial.
Ebrahimi H, Meza L, Lee K, Malhotra J, Alcantara M, Zengin Z, Dizman N, Govindarajan A, Hsu J, Llamas-Quitiquit M, Chawla N, Castro D, Mercier B, Liu S, Chehrazi-Raffle A, Dorff T, Frankel P, Li X, Pal S, Tripathi A. Effect of CBM588 in combination with cabozantinib plus nivolumab for patients (pts) with metastatic renal cell carcinoma (mRCC): A randomized clinical trial. Journal Of Clinical Oncology 2023, 41: lba104-lba104. DOI: 10.1200/jco.2023.41.17_suppl.lba104.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaProgression-free survivalTyrosine kinase inhibitorsPrimary endpointClinical outcomesStool specimensDual immune checkpoint inhibitorsMedian progression-free survivalImproved progression-free survivalOne-sided type I errorBifidobacterium sppGrade 3/4 toxicitiesImmune checkpoint inhibitorsStudy's primary endpointWeeks of treatmentDose/scheduleRandomized clinical trialsRenal cell carcinomaEligible ptsPo bidSystemic immunomodulationCheckpoint inhibitorsSecondary endpointsLine therapyMetastatic disease