2024
1968P Study EV-103 dose escalation/cohort A (DE/A): 5y follow-up of first-line (1L) enfortumab vedotin (EV) + pembrolizumab (P) in cisplatin (CIS)-ineligible locally advanced or metastatic urothelial carcinoma (la/mUC)
Rosenberg J, Petrylak D, Flaig T, Hoimes C, Gupta S, O'Donnell P, Mar N, Friedlander T, Tagawa S, Bilen M, Brown J, McKay R, Merchan J, Srinivas S, Shetty A, Moreno B, Davis G, Wirtz H, Zhu Y, Milowsky M. 1968P Study EV-103 dose escalation/cohort A (DE/A): 5y follow-up of first-line (1L) enfortumab vedotin (EV) + pembrolizumab (P) in cisplatin (CIS)-ineligible locally advanced or metastatic urothelial carcinoma (la/mUC). Annals Of Oncology 2024, 35: s1139-s1140. DOI: 10.1016/j.annonc.2024.08.2053.Peer-Reviewed Original ResearchPatient-reported outcomes (PROs) from a randomized, phase 3 trial of enfortumab vedotin plus pembrolizumab (EV+P) versus platinum-based chemotherapy (PBC) in previously untreated locally advanced or metastatic urothelial cancer (la/mUC).
Kikuchi E, Gupta S, Loriot Y, Van Der Heijden M, Bedke J, Valderrama B, Flechon A, Petrylak D, De Santis M, Galsky M, Lee J, Swami U, Sridhar S, De Giorgi U, Wright P, Lu Y, Guan X, Dillon R, Homet Moreno B, Powles T. Patient-reported outcomes (PROs) from a randomized, phase 3 trial of enfortumab vedotin plus pembrolizumab (EV+P) versus platinum-based chemotherapy (PBC) in previously untreated locally advanced or metastatic urothelial cancer (la/mUC). Journal Of Clinical Oncology 2024, 42: 108-108. DOI: 10.1200/jco.2024.42.23_suppl.108.Peer-Reviewed Original ResearchTime to pain progressionPlatinum-based chemotherapyPatient-reported outcomesBPI-SFPatients treated with platinum-based chemotherapyMedian time to pain progressionBrief Pain Inventory Short FormMetastatic urothelial cancerProgression-free survivalKaplan-Meier methodPhase 3 trialSurvival follow-upPatient-reported outcome assessmentsEnfortumab vedotinOverall survivalPain progressionTransient worseningUrothelial cancerPost-progressionQuality of Life QuestionnaireSevere painImproved survivalWorst painFollow-upWeek 4Study EV-103: Neoadjuvant treatment with enfortumab vedotin monotherapy in cisplatin-ineligible patients with muscle invasive bladder cancer (MIBC)—2-year event-free survival and safety data for Cohort H.
O'Donnell P, Hoimes C, Rosenberg J, Petrylak D, Mar N, Barata P, Srinivas S, Gourdin T, Henry E, Bilen M, George S, Rao S, Assikis V, Burgess E, Lewis B, Bowman I, Brancato S, Mildiner-Earley S, Zhu Y, Flaig T. Study EV-103: Neoadjuvant treatment with enfortumab vedotin monotherapy in cisplatin-ineligible patients with muscle invasive bladder cancer (MIBC)—2-year event-free survival and safety data for Cohort H. Journal Of Clinical Oncology 2024, 42: 4564-4564. DOI: 10.1200/jco.2024.42.16_suppl.4564.Peer-Reviewed Original ResearchPathological complete responsePathologic complete response ratePathological downstaging ratePathological downstagingEnfortumab vedotinEV treatmentUrothelial cancerPelvic lymph node dissectionAntitumor activityCisplatin-ineligible patientsNeoadjuvant treatment optionsPhase 1b/2 studyCentral pathology reviewMetastatic urothelial cancerLymph node dissectionEvent-free survivalCancer-related therapyAntibody-drug conjugatesStage cT2Improved OSComplete responseECOG PSNeoadjuvant treatmentCisplatin-ineligibleNode dissectionA phase 2/3 study of Bicycle toxin conjugate BT8009 targeting nectin-4 in patients with locally advanced or metastatic urothelial cancer (la/mUC): Duravelo-2.
Loriot Y, Siefker-Radtke A, Friedlander T, Necchi A, Wei A, Sridhar S, Garmezy B, Arroyo S, Gartside E, Liu J, Campbell C, Bader J, Petrylak D. A phase 2/3 study of Bicycle toxin conjugate BT8009 targeting nectin-4 in patients with locally advanced or metastatic urothelial cancer (la/mUC): Duravelo-2. Journal Of Clinical Oncology 2024, 42: tps4619-tps4619. DOI: 10.1200/jco.2024.42.16_suppl.tps4619.Peer-Reviewed Original ResearchUrothelial cancerMonomethyl auristatin ECohort 2Cohort 1Nectin-4Optimal doseExposure to normal tissuesInterim analysisBlinded independent central reviewMetastatic urothelial cancerObjective response ratePenetrate solid tumorsAdequate organ functionDisease control rateProgression-free survivalPlatinum-based chemotherapyDuration of responseECOG performance statusPreliminary antitumor activityIndependent central reviewPlasma half-lifeWeeks follow-upMetastatic UCRECIST v1.1Enfortumab vedotinA phase III randomized trial of eribulin (E) with gemcitabine (G) vs standard of care (SOC) for patients (pts) with metastatic urothelial carcinoma (mUC) refractory to or ineligible for PD/PDL1 antibody (Ab): SWOG S1937 updated design.
Sadeghi S, Plets M, Lara P, Tangen C, Berg S, Brown J, Bangs R, Nakagawa D, Daneshmand S, Ian M. Jr., Flaig T, Petrylak D, Lerner S. A phase III randomized trial of eribulin (E) with gemcitabine (G) vs standard of care (SOC) for patients (pts) with metastatic urothelial carcinoma (mUC) refractory to or ineligible for PD/PDL1 antibody (Ab): SWOG S1937 updated design. Journal Of Clinical Oncology 2024, 42: tps4617-tps4617. DOI: 10.1200/jco.2024.42.16_suppl.tps4617.Peer-Reviewed Original ResearchProgression free survivalMetastatic urothelial carcinomaMedian progression free survivalStandard of careOverall survivalEnfortumab vedotinSacituzumab govitecanFree survivalCisplatin-ineligible metastatic urothelial carcinomaPhase III randomized trialMedian overall survivalStudies of eribulinEndpoint of OSFGFR alterationsLiver metastasesSystemic therapyEligible ptsUrothelial carcinomaPrimary endpointGenitourinary cancersTreatment changesEribulinResponse rateActivity of EORRPatient-reported outcomes (PROs) from a randomized, phase 3 trial of enfortumab vedotin plus pembrolizumab (EV+P) versus platinum-based chemotherapy (PBC) in previously untreated locally advanced or metastatic urothelial cancer (la/mUC).
Gupta S, Loriot Y, Van Der Heijden M, Bedke J, Valderrama B, Kikuchi E, Flechon A, Petrylak D, De Santis M, Galsky M, Lee J, Swami U, Sridhar S, De Giorgi U, Wright P, Lu Y, Guan X, Dillon R, Homet Moreno B, Powles T. Patient-reported outcomes (PROs) from a randomized, phase 3 trial of enfortumab vedotin plus pembrolizumab (EV+P) versus platinum-based chemotherapy (PBC) in previously untreated locally advanced or metastatic urothelial cancer (la/mUC). Journal Of Clinical Oncology 2024, 42: 4502-4502. DOI: 10.1200/jco.2024.42.16_suppl.4502.Peer-Reviewed Original ResearchTime to pain progressionPlatinum-based chemotherapyPatient-reported outcomesBPI-SFMedian time to pain progressionPatients treated with platinum-based chemotherapyBrief Pain Inventory Short FormMetastatic urothelial cancerProgression-free survivalKaplan-Meier methodPhase 3 trialSurvival follow-upPatient-reported outcome assessmentsEnfortumab vedotinOverall survivalPain progressionTransient worseningUrothelial cancerQuality of Life QuestionnairePost-progressionSevere painImproved survivalWorst painFollow-upGlobal health status/qualityImpact 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 responseEfficacy of Antibody Drug Conjugates Alone and in Combination with other Agents in Metastatic Urothelial Carcinoma: A Scoping Review
Grant M, Stockhammer P, Austin M, Nemeth Z, Petrylak D. Efficacy of Antibody Drug Conjugates Alone and in Combination with other Agents in Metastatic Urothelial Carcinoma: A Scoping Review. Bladder Cancer 2024, 10: 9-23. PMID: 38993528, PMCID: PMC11181835, DOI: 10.3233/blc-230070.Peer-Reviewed Original ResearchMetastatic urothelial carcinomaAntibody-drug conjugatesClinical trialsUrothelial carcinomaCombination regimensDrug conjugatesSystematic reviewAnti-PD-1 agentsProspective therapeutic clinical trialsCochrane Central TrialsClinical trial cohortObjective response rateTherapeutic clinical trialsMeta-Analyses (PRISMA) statementNon-duplicated articlesPreferred Reporting ItemsComprehensive systematic reviewPotent cytotoxic payloadTrial cohortEnfortumab vedotinOvid EmbaseSacituzumab govitecanADC targetImpressive efficacyOvid MEDLINEPatient-Reported Outcomes in Patients With Advanced Urothelial Cancer Who Are Ineligible for Cisplatin and Treated With First-Line Enfortumab Vedotin Alone or With Pembrolizumab
Milowsky M, O'Donnell P, Hoimes C, Petrylak D, Flaig T, Moon H, Friedlander T, Mar N, McKay R, Srinivas S, Gravis G, Ramamurthy C, Bupathi M, Bracarda S, Wright P, Hepp Z, Carret A, Yu Y, Dillon R, Kataria R, Beaumont J, Purnajo I, Rosenberg J. Patient-Reported Outcomes in Patients With Advanced Urothelial Cancer Who Are Ineligible for Cisplatin and Treated With First-Line Enfortumab Vedotin Alone or With Pembrolizumab. Journal Of Clinical Oncology 2024, 42: 1403-1414. PMID: 38215355, PMCID: PMC11095879, DOI: 10.1200/jco.23.01547.Peer-Reviewed Original ResearchBPI-SF worst painPatient-reported outcomesEnfortumab vedotinEORTC QLQ-C30 quality of lifeBPI-SFQuality of lifeCisplatin-ineligibleUrothelial cancerWorst painTreatment armsBrief Pain Inventory Short FormAdvanced urothelial cancerPhase Ib/II trialBaseline to weekPatient-reported outcomes analysisAssociated with preservationTreatment of Cancer Quality of Life Questionnaire-Core QuestionnairePatients' quality of lifeSmall-to-moderate improvementsClinically meaningful improvementsPatient-reported outcome instrumentsEuropean Organization for Research and TreatmentEORTC QLQ-C30First-lineClinical outcomes
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
2019
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
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-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 chemotherapyPT126 A phase 3 study to evaluate enfortumab vedotin (EV) versus chemotherapy in patients with previously treated locally advanced or metastatic urothelial cancer (la/mUC): EV-301, a trial-in-progress
Petrylak D, Rosenberg J, Duran I, Loriot Y, Sonpavde G, Wu C, Gartner E, Melhem-Bertrandt A, Powles T. PT126 A phase 3 study to evaluate enfortumab vedotin (EV) versus chemotherapy in patients with previously treated locally advanced or metastatic urothelial cancer (la/mUC): EV-301, a trial-in-progress. European Urology Open Science 2019, 18: e1836-e1837. DOI: 10.1016/s1569-9056(19)31330-2.Peer-Reviewed Original Research