2023
EV-301 long-term outcomes: 24-month findings from the phase III 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. EV-301 long-term outcomes: 24-month findings from the phase III trial of enfortumab vedotin versus chemotherapy in patients with previously treated advanced urothelial carcinoma☆. Annals Of Oncology 2023, 34: 1047-1054. PMID: 37678672, DOI: 10.1016/j.annonc.2023.08.016.Peer-Reviewed Original ResearchConceptsProgression-free survivalEnfortumab vedotinAdverse eventsUrothelial carcinomaTreatment-related adverse event ratesMeaningful overall survival benefitPrior platinum-containing chemotherapyWhite blood cell countEvent ratesAdvanced urothelial carcinomaMetastatic urothelial carcinomaOverall survival benefitPeripheral sensory neuropathyPlatinum-containing chemotherapyNew safety signalsPhase III trialsAdverse event ratesRisk of deathBlood cell countIII trialsMaculopapular rashNeutrophil countObjective responseOverall survivalSurvival benefit
2022
Efficacy and safety of pembrolizumab in metastatic urothelial carcinoma: results from KEYNOTE-045 and KEYNOTE-052 after up to 5 years of follow-up ☆
Balar A, Castellano D, Grivas P, Vaughn D, Powles T, Vuky J, Fradet Y, Lee J, Fong L, Vogelzang N, Climent M, Necchi A, Petrylak D, Plimack E, Xu J, Imai K, Moreno B, Bellmunt J, de Wit R, O’Donnell P. Efficacy and safety of pembrolizumab in metastatic urothelial carcinoma: results from KEYNOTE-045 and KEYNOTE-052 after up to 5 years of follow-up ☆. Annals Of Oncology 2022, 34: 289-299. PMID: 36494006, DOI: 10.1016/j.annonc.2022.11.012.Peer-Reviewed Original ResearchConceptsMetastatic urothelial carcinomaBlinded independent central reviewCisplatin-ineligible patientsObjective response rateRECIST version 1.1Years of followUrothelial carcinomaKEYNOTE-045KEYNOTE-052Primary endpointMost treatment-related adverse eventsResponse rateSurvival rateConfirmed objective response rateTreatment-related adverse eventsProgression-free survival ratesFurther safety concernsPlatinum-containing chemotherapyFirst-line therapyImmune checkpoint inhibitorsNew safety signalsProgression-free survivalDurability of responseFirst-line pembrolizumabOverall survival rateLong-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
Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors: An updated analysis of EV-201 Cohort 2.
McGregor B, Balar A, Rosenberg J, Van Der Heijden M, Park H, Lee J, Kojima T, Harrison M, Heath E, Stein M, Loriot Y, Necchi A, Steinberg J, Liang S, Trowbridge J, Petrylak D, Yu E. Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors: An updated analysis of EV-201 Cohort 2. Journal Of Clinical Oncology 2021, 39: 4524-4524. DOI: 10.1200/jco.2021.39.15_suppl.4524.Peer-Reviewed Original ResearchBlinded independent central reviewObjective response rateProgression-free survivalDuration of responseComplete responsePD-1/PD-L1 inhibitorsPrimary analysisConfirmed objective response rateCisplatin-ineligible patientsMetastatic urothelial cancerMetastatic urothelial carcinomaOverall survival benefitPeripheral sensory neuropathyPlatinum-containing chemotherapyNew safety signalsPD-L1 inhibitorsIndependent central reviewPrimary tumor siteOnset of responseAntibody-drug conjugatesPrior platinumPrimary endpointRECIST 1.1Secondary endpointsAdverse eventsAvelumab 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 subtypesPrimary results of EV-301: A phase III trial of enfortumab vedotin versus chemotherapy in patients with previously treated locally advanced or metastatic urothelial carcinoma.
Powles T, Rosenberg J, Sonpavde G, Loriot Y, Duran I, Lee J, Matsubara N, Vulsteke C, Wu C, Campbell M, Matsangou M, Petrylak D. Primary results of EV-301: A phase III trial of enfortumab vedotin versus chemotherapy in patients with previously treated locally advanced or metastatic urothelial carcinoma. Journal Of Clinical Oncology 2021, 39: 393-393. DOI: 10.1200/jco.2021.39.6_suppl.393.Peer-Reviewed Original ResearchDisease control rateObjective response rateProgression-free survivalMetastatic urothelial carcinomaPlatinum-containing chemotherapyPhase III studyOverall survivalUrothelial carcinomaChemotherapy groupIII studyInterim analysisInvestigator-assessed progression-free survivalOpen-label phase III studyPD-1/L1 inhibitorsPrior platinum-containing chemotherapyTreatment-related adverse eventsRandomized phase III studyWhite blood cell countMaculo-papular rashPrespecified interim analysisRobust clinical benefitTolerable safety profileMedian overall survivalPhase III trialsRate of gradeEV-201 Cohort 2: Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors.
Balar A, McGregor B, Rosenberg J, Van Der Heijden M, Park S, Lee J, Harrison M, Heath E, Stein M, Loriot Y, Necchi A, Steinberg J, Liang S, Kim E, Trowbridge J, Campbell M, Petrylak D, Yu E. EV-201 Cohort 2: Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors. Journal Of Clinical Oncology 2021, 39: 394-394. DOI: 10.1200/jco.2021.39.6_suppl.394.Peer-Reviewed Original ResearchPD-1/L1Blinded independent central reviewObjective response rateProgression-free survivalDuration of responseOverall survivalPD-1/L1 inhibitorsPD-1/PD-L1 inhibitorsConfirmed objective response rateCisplatin-ineligible patientsECOG PS 2Metastatic urothelial cancerMetastatic urothelial carcinomaPeripheral sensory neuropathyPlatinum-containing chemotherapySevere renal impairmentPD-L1 inhibitorsIndependent central reviewPrimary tumor siteCohort 1 dataAntibody-drug conjugatesAdult ptsPrior platinumRECIST 1.1Last doseAvelumab (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
Study EV-103: Durability results of enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinoma.
Rosenberg J, Flaig T, Friedlander T, Milowsky M, Srinivas S, Petrylak D, Merchan J, Bilen M, Carret A, Yuan N, Sasse C, Hoimes C. Study EV-103: Durability results of enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinoma. Journal Of Clinical Oncology 2020, 38: 5044-5044. DOI: 10.1200/jco.2020.38.15_suppl.5044.Peer-Reviewed Original ResearchMetastatic urothelial carcinomaPD-1/PD-L1 inhibitorsPD-L1 inhibitorsAdverse eventsUrothelial carcinomaDay 1Common treatment-emergent adverse eventsTreatment-emergent adverse eventsCisplatin-ineligible patientsSafety/tolerabilityFirst-line settingManageable safety profilePeripheral sensory neuropathyPlatinum-containing chemotherapyTumor response ratePD-L1 statusMedian DoRMedian OSMedian PFSPFS ratesRECIST v1.1Primary endpointLiver metastasesOS ratesPD-L1Study EV-103: New randomized cohort testing enfortumab vedotin as monotherapy or in combination with pembrolizumab in locally advanced or metastatic urothelial cancer.
Mar N, Friedlander T, Hoimes C, Flaig T, Bilen M, Balar A, Henry E, Srinivas S, Rosenberg J, Petrylak D, Burgess E, Merchan J, Tagawa S, Carret A, Steinberg J, Chaney M, Milowsky M. Study EV-103: New randomized cohort testing enfortumab vedotin as monotherapy or in combination with pembrolizumab in locally advanced or metastatic urothelial cancer. Journal Of Clinical Oncology 2020, 38: tps5092-tps5092. DOI: 10.1200/jco.2020.38.15_suppl.tps5092.Peer-Reviewed Original ResearchPD-1/PD-L1 inhibitorsPlatinum-containing chemotherapyMetastatic urothelial cancerPD-L1 inhibitorsRECIST v1.1Investigator assessmentUrothelial cancerMicrotubule-disrupting agent monomethyl auristatin EDay 1PD-1 inhibitor pembrolizumabActive CNS metastasesCisplatin-containing therapyFirst-line patientsPrior systemic treatmentPD-L1 statusTumor response rateMonomethyl auristatin EAntibody-drug conjugatesMeasurable diseaseCNS metastasisPrimary endpointSecondary endpointsCreatinine clearanceSystemic treatmentUncontrolled diabetes
2019
223TiP EV-301: A phase III trial in progress evaluating enfortumab vedotin versus chemotherapy in patients with locally advanced or metastatic urothelial carcinoma
Petrylak D, Rosenberg J, Lee J, Yonese J, Duran I, Loriot Y, Sonpavde G, Wu C, Gartner E, Melhem-Bertrandt A, Powles T. 223TiP EV-301: A phase III trial in progress evaluating enfortumab vedotin versus chemotherapy in patients with locally advanced or metastatic urothelial carcinoma. Annals Of Oncology 2019, 30: ix75-ix76. DOI: 10.1093/annonc/mdz425.014.Peer-Reviewed Original ResearchMetastatic urothelial carcinomaSeattle GeneticsUrothelial carcinomaDisease progressionCohort 1Microtubule-disrupting agent monomethyl auristatin EDay 1Prior platinum-containing chemotherapyClinical care optionsRadiological disease progressionSafety/tolerabilityTumour response statusPlatinum-containing chemotherapyPhase 2 studyPhase 3 trialPhase III trialsSanofi-AventisPlatinum-based chemotherapyCurrent treatment optionsIndependent central reviewHumanized monoclonal antibodyMonomethyl auristatin ELower survival rateMedian DoRPrimary endpoint921P Quality of life of metastatic urothelial cancer (mUC) patients treated with enfortumab vedotin (EV) following platinum-containing chemotherapy and a checkpoint inhibitor (CPI): Data from EV-201 cohort 1
McGregor B, O’Donnell P, Balar A, Petrylak D, Rosenberg J, Yu E, Quinn D, Shah S, Pinelli J, Hepp Z, Galsky M. 921P Quality of life of metastatic urothelial cancer (mUC) patients treated with enfortumab vedotin (EV) following platinum-containing chemotherapy and a checkpoint inhibitor (CPI): Data from EV-201 cohort 1. Annals Of Oncology 2019, 30: v367-v368. DOI: 10.1093/annonc/mdz249.020.Peer-Reviewed Original ResearchBristol-Myers SquibbGenentech/RochePlatinum-containing chemotherapyEnfortumab vedotinVisual analog scaleCheckpoint inhibitorsCohort 1EMD SeronoSeattle GeneticsAstellas Pharma Inc.Metastatic urothelial cancer patientsPatient-reported outcome measuresSelf-rated health statusPain/discomfortUrothelial cancer patientsGreater symptom burdenAnxiety/depressionEQ-5D utilitiesMUC patientsPrior chemotherapyExploratory endpointsSymptom burdenVAS scoresCancer QualityCycle 5EV-201: Results of enfortumab vedotin monotherapy for locally advanced or metastatic urothelial cancer previously treated with platinum and immune checkpoint inhibitors.
Petrylak D, Balar A, O'Donnell P, McGregor B, Heath E, Yu E, Galsky M, Hahn N, Gartner E, Pinelli J, Melhem-Bertrandt A, Rosenberg J. EV-201: Results of enfortumab vedotin monotherapy for locally advanced or metastatic urothelial cancer previously treated with platinum and immune checkpoint inhibitors. Journal Of Clinical Oncology 2019, 37: 4505-4505. DOI: 10.1200/jco.2019.37.18_suppl.lba4505.Peer-Reviewed Original ResearchTreatment-related AEsMetastatic urothelial cancerCheckpoint inhibitorsDuration of responseLiver metastasesUrothelial cancerCohort 1Common treatment-related AEsBlinded independent central reviewImmune checkpoint inhibitorsManageable safety profilePlatinum-containing chemotherapyPhase 1 trialLimited treatment optionsIndependent central reviewHigh unmet needTwo-cohort studyMUC patientsPrior chemotherapyPrior platinumRECIST 1.1Primary endpointSecondary endpointsPulmonary infectionPeripheral neuropathyEV-301: Phase III study to evaluate enfortumab vedotin (EV) versus chemotherapy in patients with previously treated locally advanced or metastatic urothelial cancer (la/mUC).
Petrylak D, Rosenberg J, Duran I, Loriot Y, Sonpavde G, Wu C, Gartner E, Melhem-Bertrandt A, Powles T. EV-301: Phase III study to evaluate enfortumab vedotin (EV) versus chemotherapy in patients with previously treated locally advanced or metastatic urothelial cancer (la/mUC). Journal Of Clinical Oncology 2019, 37: tps497-tps497. DOI: 10.1200/jco.2019.37.7_suppl.tps497.Peer-Reviewed Original ResearchObjective response rateCheckpoint inhibitorsEnfortumab vedotinDisease progressionMicrotubule-disrupting agent monomethyl auristatin EDay 1Open-label phase 3 trialResponse rateECOG performance status scorePivotal phase 2 studyPrior platinum-containing chemotherapyStandard first-line treatmentCarboplatin-based chemotherapyImmune checkpoint inhibitorsMetastatic urothelial cancerPerformance status scorePlatinum-containing chemotherapyRadiological disease progressionSafety/tolerabilityTumour response statusPhase 2 studyPhase 3 trialPhase III studyProgression-free survivalCisplatin-based chemotherapy
2018
Pembrolizumab (pembro) plus epacadostat or placebo for locally advanced or metastatic urothelial carcinoma (UC) after failure of first-line platinum-containing chemotherapy: KEYNOTE-698/ECHO-303.
Powles T, Bellmunt J, Petrylak D, Fong L, Nishiyama H, Sternberg C, Chen M, Pang L, Munteanu M, Zhao Y, Smith D. Pembrolizumab (pembro) plus epacadostat or placebo for locally advanced or metastatic urothelial carcinoma (UC) after failure of first-line platinum-containing chemotherapy: KEYNOTE-698/ECHO-303. Journal Of Clinical Oncology 2018, 36: tps4586-tps4586. DOI: 10.1200/jco.2018.36.15_suppl.tps4586.Peer-Reviewed Original ResearchUrothelial carcinomaFirst-line platinum-containing chemotherapyMetastatic urothelial carcinomaPlatinum-containing chemotherapy