2024
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.
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 EORR
2023
Enfortumab vedotin (EV) alone or in combination with pembrolizumab (P) in previously untreated cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer (la/mUC): Subgroup analyses of confirmed objective response rate (cORR) from EV-103 cohort K.
O'Donnell P, Rosenberg J, Hoimes C, Petrylak D, Milowsky M, McKay R, Srinivas S, Friedlander T, Ramamurthy C, Bilen M, Burgess E, Mar N, Moon H, Geynisman D, George S, Carret A, Yu Y, Guseva M, Moreno B, Flaig T. Enfortumab vedotin (EV) alone or in combination with pembrolizumab (P) in previously untreated cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer (la/mUC): Subgroup analyses of confirmed objective response rate (cORR) from EV-103 cohort K. Journal Of Clinical Oncology 2023, 41: 499-499. DOI: 10.1200/jco.2023.41.6_suppl.499.Peer-Reviewed Original ResearchLiver metastasesDay 1Disease sitesPD-L1 expression statusBlinded independent central reviewAppropriate dose modificationCisplatin-ineligible patientsManageable safety profileMetastatic urothelial cancerObjective response rateECOG PS scorePhase 3 trialPre-specified subgroupsPrimary disease siteDuration of responseIndependent central reviewMetastatic disease sitesHigh unmet needECOG PSMedian DoRRECIST v1.1Untreated LAOverall cohortPrimary endpointSecondary endpoints
2021
Quality of life, functioning, and symptoms in patients with previously treated locally advanced or metastatic urothelial carcinoma from EV-301: A randomized phase 3 trial of enfortumab vedotin versus chemotherapy.
Mamtani R, Rosenberg J, Powles T, Sonpavde G, Loriot Y, Duran I, Lee J, Matsubara N, Vulsteke C, Castellano D, Sridhar S, Pappot H, Valderrama B, Gurney H, Bedke J, Van Der Heijden M, Wu C, Hepp Z, McKay C, Petrylak D. Quality of life, functioning, and symptoms in patients with previously treated locally advanced or metastatic urothelial carcinoma from EV-301: A randomized phase 3 trial of enfortumab vedotin versus chemotherapy. Journal Of Clinical Oncology 2021, 39: 4539-4539. DOI: 10.1200/jco.2021.39.15_suppl.4539.Peer-Reviewed Original ResearchMetastatic urothelial carcinomaUrothelial carcinomaOpen-label phase 3 studyCompliance rateGlobal health status scaleRandomized phase 3 trialSymptom scales/itemsLife Questionnaire Core 30Median overall survivalQuestionnaire compliance ratesPhase 3 studyPhase 3 trialCancer Core QualityWeeks of treatmentHealth status scalesRisk of deathQLQ-C30 scoresQLQ-C30 domainsQuality of lifeBenefit/riskScales/itemsPain symptomsAppetite lossLiver metastasesOverall survival
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: Preliminary 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: Preliminary durability results of enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinoma. Journal Of Clinical Oncology 2020, 38: 441-441. DOI: 10.1200/jco.2020.38.6_suppl.441.Peer-Reviewed Original ResearchMetastatic urothelial carcinomaAdverse eventsUrothelial carcinomaDay 1Common treatment-emergent adverse eventsPD-1/PD-L1 inhibitorsTreatment-emergent adverse eventsSafety/tolerabilityFirst-line settingManageable safety profilePeripheral sensory neuropathyPD-L1 statusPD-L1 inhibitorsMedian DoRMedian PFSRECIST v1.1Primary endpointLiver metastasesStandard therapyPD-L1Sensory neuropathySafety profilePlatinum chemotherapyHigh patientMulticohort study
2019
EV-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 neuropathyMature results from EV-101: A phase I study of enfortumab vedotin in patients with metastatic urothelial cancer (mUC).
Rosenberg J, Sridhar S, Zhang J, Smith D, Ruether J, Flaig T, Baranda J, Lang J, Plimack E, Sangha R, Heath E, Merchan J, Quinn D, Srinivas S, Milowsky M, Wu C, Gartner E, Melhem-Bertrandt A, Petrylak D. Mature results from EV-101: A phase I study of enfortumab vedotin in patients with metastatic urothelial cancer (mUC). Journal Of Clinical Oncology 2019, 37: 377-377. DOI: 10.1200/jco.2019.37.7_suppl.377.Peer-Reviewed Original ResearchMetastatic urothelial cancerTreatment-related AEsLiver metastasesMedian followUrothelial cancerPrimary tumor siteUnmet medical needMedian PFSPrior chemotherapyMonotherapy studiesMedian durationPoor prognosisCombination therapyPlatinum chemotherapyMature resultsDay 1Nectin-4Medical needTumor siteSecondary objectivePhase IAntitumor activityEncouraging responseSurvival dataChemotherapy
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 subgroupsEnfortumab vedotin (EV) in patients (Pts) with metastatic urothelial carcinoma (mUC) with prior checkpoint inhibitor (CPI) failure: A prospective cohort of an ongoing phase 1 study.
Petrylak D, Smith D, Flaig T, Zhang J, Sridhar S, Ruether J, Plimack E, Merchan J, Quinn D, Kilari D, Srinivas S, Baranda J, Lang J, Milowsky M, Galsky M, Spira A, Gartner E, Wu C, Melhem-Bertrandt A, Rosenberg J. Enfortumab vedotin (EV) in patients (Pts) with metastatic urothelial carcinoma (mUC) with prior checkpoint inhibitor (CPI) failure: A prospective cohort of an ongoing phase 1 study. Journal Of Clinical Oncology 2018, 36: 431-431. DOI: 10.1200/jco.2018.36.6_suppl.431.Peer-Reviewed Original ResearchMetastatic urothelial carcinomaOngoing phase 1 studiesPhase 1 studyLiver metastasesEvaluable ptsDisease progressionNectin-4High unmet medical needPhase 2 dosePost-baseline scanAntitumor activityMedian treatment durationPhase 2 studyPrimary tumor siteHigh unmet needUnmet medical needMonomethyl auristatin E.CPI therapyFatal AEsPrior chemotherapyPrior therapyRECIST v1.1Unconfirmed PRMetastatic settingPrimary endpointDocetaxel with or without ramucirumab after immune checkpoint inhibition in platinum-refractory metastatic urothelial carcinoma (mUC): Prespecified subgroup analysis from the phase 3 RANGE trial.
Drakaki A, Kirby C, Van Der Heijden M, Petrylak D, Powles T, Chi K, Flechon A, Necchi A, Geczi L, Lee J, Gakis G, Bracarda S, Chowdhury S, Lin C, Keizman D, Vaishampayan U, Liepa A, Zimmermann A, Bell-McGuinn K, Castellano D. Docetaxel with or without ramucirumab after immune checkpoint inhibition in platinum-refractory metastatic urothelial carcinoma (mUC): Prespecified subgroup analysis from the phase 3 RANGE trial. Journal Of Clinical Oncology 2018, 36: 434-434. DOI: 10.1200/jco.2018.36.6_suppl.434.Peer-Reviewed Original ResearchPlatinum-refractory metastatic urothelial carcinomaImmune checkpoint inhibitorsMetastatic urothelial carcinomaObjective response ratePrior immune checkpoint inhibitorsLiver metastasesPD-L1Subgroup analysisDouble-blinded phase 3 trialPD-1/PD-L1Disease sitesHigher objective response ratePre-specified subgroup analysisInvestigator-assessed PFSImmune checkpoint inhibitionProgression-free survivalPhase 3 trialPrespecified subgroup analysisPlatinum-based chemotherapyFrequency of gradeICI therapyMedian PFSSecondary endpointsCheckpoint inhibitorsData cutoff
2017
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).
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
2015
Clinical activity, safety, and biomarkers of MPDL3280A in metastatic urothelial bladder cancer: Additional analysis from phase IA study.
Kim J, Bellmunt J, Powles T, Loriot Y, Vogelzang N, Cruz Zambrano C, Burris H, Teng S, Shen X, Bruey J, Boyd Z, Hegde P, Petrylak D. Clinical activity, safety, and biomarkers of MPDL3280A in metastatic urothelial bladder cancer: Additional analysis from phase IA study. Journal Of Clinical Oncology 2015, 33: 297-297. DOI: 10.1200/jco.2015.33.7_suppl.297.Peer-Reviewed Original ResearchUrothelial bladder cancerMetastatic urothelial bladder cancerPD-L1 expressionBladder cancerImmune-mediated antitumor responsePD-L1/PDPhase Ia studyTreatment-related AEsTreatment-related deathsTumor burden markersTumor gene expressionIHC 0/1Median DoRPrior platinumPt ageRECIST v1.1Median PFSPrior therapyData cutoffDurable responsesExpansion cohortInflammatory markersLiver metastasesPD-L1Antitumor response
2014
808O Inhibition of Pd-L1 By Mpdl3280A Leads to Clinical Activity in Pts with Metastatic Urothelial Bladder Cancer (Ubc)
Bellmunt J, Petrylak D, Powles T, Braiteh F, Vogelzang N, Cruz C, Burris H, Eder J, Fine G, Teng M, Shen X, Bruey J, Boyd Z, Hegde P, Chen D, Loriot Y. 808O Inhibition of Pd-L1 By Mpdl3280A Leads to Clinical Activity in Pts with Metastatic Urothelial Bladder Cancer (Ubc). Annals Of Oncology 2014, 25: iv280. DOI: 10.1093/annonc/mdu337.1.Peer-Reviewed Original ResearchMedian durationPD-L1Metastatic urothelial bladder cancerCaris Life SciencesClinical cutoff dateDrug-related AEsECOG PS 1Employees of GenentechPD-L1 statusPD-L1 expressionPoor prognostic factorReceptor PD-1Urothelial bladder cancerPD-L1 IHCPD-L1 bindingEvaluable ptsIHC 0/1Median DoRPrior chemoPrior cisplatinPrior therapyRECIST v1.1Visceral metastasesLiver metastasesObjective response
2012
Time from prior chemotherapy (TFPC) as a prognostic factor in advanced urothelial carcinoma (UC) receiving second-line systemic therapy.
Pond G, Sonpavde G, Choueiri T, Qu A, Vaughn D, Fougeray R, Niegisch G, Albers P, Wong Y, Ko Y, Sridhar S, Galsky M, Petrylak D, Beer T, Stadler W, O'Donnell P, Sternberg C, Rosenberg J, Molins J. Time from prior chemotherapy (TFPC) as a prognostic factor in advanced urothelial carcinoma (UC) receiving second-line systemic therapy. Journal Of Clinical Oncology 2012, 30: 4522-4522. DOI: 10.1200/jco.2012.30.15_suppl.4522.Peer-Reviewed Original ResearchSecond-line therapyAdvanced urothelial carcinomaMedian overall survivalOverall survivalPrior chemotherapyUrothelial carcinomaLiver metastasesPerformance statusPrognostic factorsSecond-line systemic therapyOptimal cutpointSignificant negative prognostic impactECOG performance statusFirst study treatmentSecond-line chemotherapyPhase II trialKaplan-Meier methodNegative prognostic impactProportional hazards regressionLikelihood ratio χBaseline HbII trialMetastatic diseaseOS independentPrognostic impact
2006
Pharmacokinetics (PK), safety and tolerability of atrasentan (ABT-627, ATN) in combination with docetaxel (DOC) in men with hormone refractory prostate cancer (HRPC)
Petrylak D, Mohile S, Shelton G, Carr R, Steinberg J, Sleep D, Melia J, Rieser M, Nanus D, Milowsky M. Pharmacokinetics (PK), safety and tolerability of atrasentan (ABT-627, ATN) in combination with docetaxel (DOC) in men with hormone refractory prostate cancer (HRPC). Journal Of Clinical Oncology 2006, 24: 14512-14512. DOI: 10.1200/jco.2006.24.18_suppl.14512.Peer-Reviewed Original ResearchHormone-refractory prostate cancerPSA declineAdverse eventsTreatment of HRPCPhase III clinical developmentPhase III studyRefractory prostate cancerUnexpected adverse eventsDOC infusionNeutropenic feverIII studyLiver metastasesOral dosesPO QDSelective endothelinPK interactionsReceptor antagonistPlasma concentrationsProstate cancerCYP3A4 activityClinical developmentDay 1DocetaxelPK resultsPharmacokinetics