2024
Sacituzumab Govitecan Demonstrates Efficacy across Tumor Trop-2 Expression Levels in Patients with Advanced Urothelial Cancer.
Loriot Y, Balar A, Petrylak D, Kalebasty A, Grivas P, Fléchon A, Jain R, Swami U, Bupathi M, Barthélémy P, Beuzeboc P, Palmbos P, Kyriakopoulos C, Pouessel D, Sternberg C, Tonelli J, Sierecki M, Zavodovskaya M, Elboudwarej E, Diehl L, Jürgensmeier J, Tagawa S. Sacituzumab Govitecan Demonstrates Efficacy across Tumor Trop-2 Expression Levels in Patients with Advanced Urothelial Cancer. Clinical Cancer Research 2024, 30: 3179-3188. PMID: 39086310, DOI: 10.1158/1078-0432.ccr-23-3924.Peer-Reviewed Original ResearchConceptsTrop-2 expressionTrop-2Positive tumor cellsUrothelial cancerMetastatic UCSacituzumab govitecanTumor cellsTumor samplesOpen-label phase II studyTrophoblast cell surface antigen 2Human trophoblast cell-surface antigen 2Advanced urothelial cancerSN-38 payloadPhase II studyC1-3Archival tumor samplesExpression levelsCohorts 1 to 3Surface antigen 2Antibody drug conjugatesOS benefitII studyExamined tumorsH-scoreMembrane expressionImpact of exposure on outcomes with enfortumab vedotin in patients with locally advanced or metastatic urothelial cancer.
Petrylak D, Chia Y, Yu E, Powles T, Flaig T, Loriot Y, O'Donnell P, Heath E, Kojima T, Park S, Sonpavde G, Picus J, Matsubara N, Obara W, Chudasama V, Poondru S, Harrison M, Kim E, Brancato S, Rosenberg J. Impact of exposure on outcomes with enfortumab vedotin in patients with locally advanced or metastatic urothelial cancer. Journal Of Clinical Oncology 2024, 42: 4503-4503. DOI: 10.1200/jco.2024.42.16_suppl.4503.Peer-Reviewed Original ResearchMetastatic urothelial cancerEnfortumab vedotinDose modificationEV exposureUrothelial cancerPre-dose samplesAssociated with lower riskPopulation PK modelLikelihood of responseEV-201Median PFSOS benefitOS outcomesDose reductionExposure quartilesExposure-responsePK assessmentEfficacy outcomesSafety profilePeripheral neuropathySkin reactionsPK modelLow riskSafety outcomesDose response
2022
Long-term outcomes in EV-301: 24-month findings from the phase 3 trial of enfortumab vedotin versus chemotherapy in patients with previously treated advanced urothelial carcinoma.
Rosenberg J, Powles T, Sonpavde G, Loriot Y, Duran I, Lee J, Matsubara N, Vulsteke C, Castellano D, Mamtani R, Wu C, Matsangou M, Campbell M, Petrylak D. Long-term outcomes in EV-301: 24-month findings from the phase 3 trial of enfortumab vedotin versus chemotherapy in patients with previously treated advanced urothelial carcinoma. Journal Of Clinical Oncology 2022, 40: 4516-4516. DOI: 10.1200/jco.2022.40.16_suppl.4516.Peer-Reviewed Original ResearchProgression-free survivalOverall survivalStandard chemotherapyUrothelial carcinomaInterim analysisInvestigator-assessed progression-free survivalLong-term clinical profilesPrior platinum-containing chemotherapyTreatment-related adverse eventsPrespecified interim analysisRobust clinical benefitTolerable safety profileAdvanced urothelial carcinomaMedian overall survivalMetastatic urothelial carcinomaPlatinum-containing chemotherapyNew safety signalsPhase 3 trialRate of gradeLonger overall survivalLong-term outcomesStandard of careAntibody-drug conjugatesConsistent survival advantageOS benefitAvelumab first-line (1L) maintenance for advanced urothelial carcinoma (UC): Long-term follow-up results from the JAVELIN Bladder 100 trial.
Powles T, Park H, Voog E, Caserta C, Pérez-Valderrama B, Gurney H, Loriot Y, Sridhar S, Tsuchiya N, Sternberg C, Bellmunt J, Aragon-Ching J, Petrylak D, Blake-Haskins A, Laliberte R, Wang J, Costa N, Grivas P. Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (UC): Long-term follow-up results from the JAVELIN Bladder 100 trial. Journal Of Clinical Oncology 2022, 40: 487-487. DOI: 10.1200/jco.2022.40.6_suppl.487.Peer-Reviewed Original ResearchBest supportive careAdvanced urothelial carcinomaProgression-free survivalPlatinum-containing chemotherapyUrothelial carcinomaOverall survivalPD-L1Metastatic urothelial carcinomaNew safety signalsLonger overall survivalLong-term followStandard of careLong-term safetyFirst-line maintenanceAnticancer drug therapyOS benefitProlonged OSMonotherapy studiesPrimary endpointSecondary endpointsAlone armPrespecified subgroupsSupportive careTreatment guidelinesDrug therapy
2021
Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (UC): Analysis of clinical and genomic subgroups from the JAVELIN Bladder 100 trial.
Powles T, Petrylak D, Park H, Sridhar S, Caserta C, Vuillemin A, Lee H, Bellmunt J, Yamamoto Y, Aragon-Ching J, Huang B, Ching K, Davis C, Di Pietro A, Loriot Y, Grivas P. Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (UC): Analysis of clinical and genomic subgroups from the JAVELIN Bladder 100 trial. Journal Of Clinical Oncology 2021, 39: 4520-4520. DOI: 10.1200/jco.2021.39.15_suppl.4520.Peer-Reviewed Original ResearchBest supportive careAdvanced urothelial carcinomaOverall survivalUrothelial carcinomaPD-L1OS benefitGenomic subtypesMetastatic urothelial carcinomaPlatinum-containing chemotherapyPlatinum-based chemotherapyProlonged overall survivalStandard of careFirst-line maintenanceGenomic subgroupsSubgroups of interestBSC armEligible ptsUnresectable diseasePrimary endpointSupportive careCancer Genome AtlasLymph nodesTract tumorsDisease stageTCGA subtypesPembrolizumab (pembro) versus investigator’s choice of paclitaxel, docetaxel, or vinflunine in recurrent, advanced urothelial cancer (UC): 5-year follow-up from the phase 3 KEYNOTE-045 trial.
Bellmunt J, Necchi A, De Wit R, Lee J, Fong L, Vogelzang N, Durán M, Petrylak D, Choueiri T, Gerritsen W, Gurney H, Quinn D, Culine S, Sternberg C, Xu J, Moreno B, Godwin J, Bajorin D, Vaughn D, Fradet Y. Pembrolizumab (pembro) versus investigator’s choice of paclitaxel, docetaxel, or vinflunine in recurrent, advanced urothelial cancer (UC): 5-year follow-up from the phase 3 KEYNOTE-045 trial. Journal Of Clinical Oncology 2021, 39: 4532-4532. DOI: 10.1200/jco.2021.39.15_suppl.4532.Peer-Reviewed Original ResearchDuration of responseMetastatic urothelial cancerUrothelial cancerKEYNOTE-045Median OSOS benefitInvestigator's choiceKey secondary end pointMedian DOREnd pointAdvanced urothelial cancerECOG PS 0Platinum-containing regimenPrimary end pointSecondary end pointsTreatment-related AEsPhase 3 trialYears of therapyRECIST v1.1Baseline hemoglobinECOG PSMeasurable diseaseOS ratesPrior therapyData cutoffAvelumab (Ave) first-line (1L) maintenance plus best supportive care (BSC) versus BSC alone for advanced urothelial carcinoma (UC): JAVELIN Bladder 100 subgroup analysis based on duration and cycles of 1L chemotherapy.
Loriot Y, Powles T, Climent Durán M, Sridhar S, Bellmunt J, Petrylak D, Wang J, Costa N, Laliberte R, Di Pietro A, Grivas P, Sternberg C. Avelumab (Ave) first-line (1L) maintenance plus best supportive care (BSC) versus BSC alone for advanced urothelial carcinoma (UC): JAVELIN Bladder 100 subgroup analysis based on duration and cycles of 1L chemotherapy. Journal Of Clinical Oncology 2021, 39: 438-438. DOI: 10.1200/jco.2021.39.6_suppl.438.Peer-Reviewed Original ResearchBest supportive careAdvanced urothelial carcinomaOverall survivalUrothelial carcinomaOS benefitUnstratified Cox proportional hazards modelProgression-free survival benefitCox proportional hazards modelMetastatic urothelial carcinomaPlatinum-containing chemotherapyDuration of chemotherapyNumber of patientsAnalysis of efficacyProportional hazards modelFirst-line maintenanceDelay/interruptionChemotherapy subgroupEligible patientsBaseline characteristicsDose intensityInvestigator's discretionSupportive careSurvival benefitTreatment armsTreatment patterns
2020
Maintenance avelumab + best supportive care (BSC) versus BSC alone after platinum-based first-line (1L) chemotherapy in advanced urothelial carcinoma (UC): JAVELIN Bladder 100 phase III interim analysis.
Powles T, Park S, Voog E, Caserta C, Valderrama B, Gurney H, Kalofonos H, Radulovic S, Demey W, Ullén A, Loriot Y, Sridhar S, Tsuchiya N, Kopyltsov E, Sternberg C, Bellmunt J, Aragon-Ching J, Petrylak D, di Pietro A, Grivas P. Maintenance avelumab + best supportive care (BSC) versus BSC alone after platinum-based first-line (1L) chemotherapy in advanced urothelial carcinoma (UC): JAVELIN Bladder 100 phase III interim analysis. Journal Of Clinical Oncology 2020, 38: lba1-lba1. DOI: 10.1200/jco.2020.38.18_suppl.lba1.Peer-Reviewed Original ResearchBest supportive careAdvanced urothelial carcinomaProgression-free survivalMedian overall survivalOverall survivalPlatinum-based chemotherapyPD-L1Urothelial carcinomaAdverse eventsSupportive carePlatinum-based first-line chemotherapyCausality adverse eventsCycles of gemcitabineFirst-line chemotherapyMetastatic urothelial carcinomaPhase 3 trialUrinary tract infectionIndependent central reviewEligible patientsNonvisceral diseaseOS benefitStable diseaseMaintenance therapyPrimary endpointSecondary endpoints
2019
927P Clinical outcomes by sex with atezolizumab (atezo) monotherapy in patients (pts) with locally advanced/metastatic urothelial carcinoma (mUC)
Hoffman-Censits J, Rosenberg J, van Der Heijden M, Dreicer R, Gracia J, Petrylak D, Retz M, Sabbatini R, Naglieri E, Caserta C, Maruzzo M, Iacovelli R, Galli L, McDermott R, Barrera R, Bonfill T, De Ducla S, Ding B, Linsenmeier J, Sternberg C. 927P Clinical outcomes by sex with atezolizumab (atezo) monotherapy in patients (pts) with locally advanced/metastatic urothelial carcinoma (mUC). Annals Of Oncology 2019, 30: v372-v373. DOI: 10.1093/annonc/mdz249.026.Peer-Reviewed Original ResearchMetastatic urothelial carcinomaBody mass indexF. Hoffmann-La RochePersonal feesBristol-Myers SquibbHoffmann-La RocheCohort 1Roche/GenentechMedian body mass indexSeattle GeneticsMedian treatment durationObjective response rateSignificant OS differenceOverall survival outcomesDifferent treatment settingsSignificant differencesBristol-Meyers SquibbAtezolizumab monotherapyECOG PSFortress BiotechMale ptsMedian OSOS benefitWeill Cornell MedicineTreatment discontinuation
2018
Pembrolizumab (pembro) versus investigator’s choice (paclitaxel, docetaxel, or vinflunine) in recurrent, advanced urothelial cancer (UC): 2-year follow-up from the phase 3 KEYNOTE-045 trial.
Fradet Y, Bellmunt J, De Wit R, Vaughn D, Lee J, Fong L, Vogelzang N, Climent M, Petrylak D, Choueiri T, Necchi A, Gerritsen W, Gurney H, Quinn D, Culine S, Sternberg C, Nam K, Frenkl T, Perini R, Bajorin D. Pembrolizumab (pembro) versus investigator’s choice (paclitaxel, docetaxel, or vinflunine) in recurrent, advanced urothelial cancer (UC): 2-year follow-up from the phase 3 KEYNOTE-045 trial. Journal Of Clinical Oncology 2018, 36: 4521-4521. DOI: 10.1200/jco.2018.36.15_suppl.4521.Peer-Reviewed Original ResearchMetastatic urothelial cancerUrothelial cancerInvestigator's choiceAdverse eventsPrimary efficacy end pointTreatment-related adverse eventsEnd pointAdvanced urothelial cancerPlatinum-containing regimenEfficacy end pointSecondary end pointsKaplan-Meier methodPlatinum-based chemotherapyRisk factor groupsBaseline hemoglobinECOG PSMedian OSOS benefitPrior therapyEligible patientsLiver metastasesMedian durationPembroInterim analysisExpression subgroupsTwo-year follow-up from the phase 3 KEYNOTE-045 trial of pembrolizumab (pembro) vs investigator’s choice (paclitaxel, docetaxel, or vinflunine) in recurrent, advanced urothelial cancer (UC).
Bellmunt J, De Wit R, Vaughn D, Fradet Y, Lee J, Fong L, Vogelzang N, Climent M, Petrylak D, Choueiri T, Necchi A, Gerritsen W, Gurney H, Quinn D, Culine S, Sternberg C, Nam K, Frenkl T, Perini R, Bajorin D. Two-year follow-up from the phase 3 KEYNOTE-045 trial of pembrolizumab (pembro) vs investigator’s choice (paclitaxel, docetaxel, or vinflunine) in recurrent, advanced urothelial cancer (UC). Journal Of Clinical Oncology 2018, 36: 410-410. DOI: 10.1200/jco.2018.36.6_suppl.410.Peer-Reviewed Original ResearchMetastatic urothelial cancerUrothelial cancerInvestigator's choiceAdverse eventsPrimary efficacy end pointTreatment-related adverse eventsEnd pointAdvanced urothelial cancerPlatinum-containing regimenEfficacy end pointSecondary end pointsKaplan-Meier methodPlatinum-based chemotherapyRisk factor groupsECOG PSBaseline hemoglobinEligible patientsMedian OSOS benefitPrior therapyMedian durationLiver metastasesPembroInterim analysisExpression subgroups
2017
Sipuleucel-T (sip-T) to induce cytolytic T lymphocyte (CTL) activity against target antigens in men with hormone-sensitive and castration-resistant prostate cancer (CRPC).
Drake C, Antonarakis E, Petrylak D, Quinn D, Kibel A, Chang N, Dearstyne E, Campogan D, Haynes H, Vu T, Sheikh N, Small E. Sipuleucel-T (sip-T) to induce cytolytic T lymphocyte (CTL) activity against target antigens in men with hormone-sensitive and castration-resistant prostate cancer (CRPC). Journal Of Clinical Oncology 2017, 35: 5046-5046. DOI: 10.1200/jco.2017.35.15_suppl.5046.Peer-Reviewed Original ResearchCastration-resistant prostate cancerPeripheral blood mononuclear cellsCTL lytic activityCD107a expressionOverall survivalT cellsImmune responseSymptomatic metastatic castration-resistant prostate cancerMetastatic castration-resistant prostate cancerCytolytic T lymphocyte activityAntigen-specific cellular responsesAutologous cellular immunotherapyGreater CTL activityHealthy donor controlsRobust CTL responsesT lymphocyte activityCD8 T cellsLonger overall survivalAntigen-specific proliferationBlood mononuclear cellsHumoral immune responseLytic activityOS benefitMCRPC patientsMetastatic CRPCPlanned survival analysis from KEYNOTE-045: Phase 3, open-label study of pembrolizumab (pembro) versus paclitaxel, docetaxel, or vinflunine in recurrent, advanced urothelial cancer (UC).
Bajorin D, De Wit R, Vaughn D, Fradet Y, Lee J, Fong L, Vogelzang N, Climent M, Petrylak D, Choueiri T, Necchi A, Gerritsen W, Gurney H, Quinn D, Culine S, Sternberg C, Mai Y, Puhlmann M, Perini R, Bellmunt J. Planned survival analysis from KEYNOTE-045: Phase 3, open-label study of pembrolizumab (pembro) versus paclitaxel, docetaxel, or vinflunine in recurrent, advanced urothelial cancer (UC). Journal Of Clinical Oncology 2017, 35: 4501-4501. DOI: 10.1200/jco.2017.35.15_suppl.4501.Peer-Reviewed Original ResearchAdvanced urothelial cancerUrothelial cancerSurvival analysisPrimary efficacy end pointEnd pointECOG PS 0Efficacy end pointSecond-line chemotherapyTreatment-related AEsOpen-label studySecondary end pointsPD-L1 expressionSuperior safety profileECOG PSKEYNOTE-045Measurable diseaseOS benefitMedian OSPrior therapyBaseline characteristicsLonger OSMedian durationPS 0Systemic therapyLiver metastases