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 expressionPatient-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
Avelumab First-line Maintenance for Advanced Urothelial Carcinoma: Analysis from JAVELIN Bladder 100 by Duration of First-line Chemotherapy and Interval Before Maintenance
Sridhar S, Powles T, Climent Durán M, Park S, Massari F, Thiery-Vuillemin A, Valderrama B, Ullén A, Tsuchiya N, Aragon-Ching J, Gupta S, Petrylak D, Bellmunt J, Wang J, Laliberte R, di Pietro A, Costa N, Grivas P, Sternberg C, Loriot Y. Avelumab First-line Maintenance for Advanced Urothelial Carcinoma: Analysis from JAVELIN Bladder 100 by Duration of First-line Chemotherapy and Interval Before Maintenance. European Urology 2023, 85: 154-163. PMID: 37714742, DOI: 10.1016/j.eururo.2023.08.001.Peer-Reviewed Original ResearchBest supportive careProgression-free survivalAdvanced urothelial carcinomaFirst-line chemotherapyPlatinum-based chemotherapyOverall survivalFirst-line maintenanceChemotherapy durationMaintenance treatmentUrothelial carcinomaFirst-line platinum-based chemotherapyAnalysis of OSAdvanced urothelial cancerPhase 3 trialAnalysis of subgroupsAdvanced UCPrior chemotherapyProspective trialSafety findingsSupportive careHazard ratioUrothelial cancerDisease progressionChemotherapyOverall populationStudy EV-103: Neoadjuvant treatment with enfortumab vedotin monotherapy in cisplatin-ineligible patients (pts) with muscle invasive bladder cancer (MIBC): Updated results for Cohort H.
Flaig T, Rosenberg J, Hoimes C, O'Donnell P, Mar N, Gourdin T, Henry S, Bilen M, George S, Barata P, Srinivas S, Rao S, Assikis V, Burgess E, Ramamurthy C, Haas G, Lukas J, Mildiner-Earley S, Yu Y, Petrylak D. Study EV-103: Neoadjuvant treatment with enfortumab vedotin monotherapy in cisplatin-ineligible patients (pts) with muscle invasive bladder cancer (MIBC): Updated results for Cohort H. Journal Of Clinical Oncology 2023, 41: 4595-4595. DOI: 10.1200/jco.2023.41.16_suppl.4595.Peer-Reviewed Original ResearchMuscle-invasive bladder cancerEvent-free survivalPhase 1b/2 studyPathological complete responseCancer-related therapyEV treatmentUrothelial cancerSafety profilePD-1/L1 inhibitorsMedian event-free survivalPelvic lymph node dissectionAdvanced urothelial cancerAntitumor activityCisplatin-ineligible patientsManageable safety profileNeoadjuvant treatment optionsOngoing phase 2Pathological downstaging ratePts underwent surgeryTolerable safety profileCentral pathology reviewKey secondary endpointLymph node dissectionPhase 3 studyInvasive bladder cancer
2021
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.
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 cutoff
2020
Association of TMB with efficacy of pembrolizumab (pembro) in patients (pts) with advanced urothelial cancer (UC): Results from KEYNOTE-045 and KEYNOTE-052
Bellmunt J, de Wit R, Fradet Y, Climent M, Petrylak D, Lee J, Fong L, Necchi A, Sternberg C, Grivas P, O’Donnell P, Powles T, Plimack E, Cristescu R, Lunceford J, Ma J, Rajasagi M, Godwin J, Moreno B, Bajorin D. Association of TMB with efficacy of pembrolizumab (pembro) in patients (pts) with advanced urothelial cancer (UC): Results from KEYNOTE-045 and KEYNOTE-052. Annals Of Oncology 2020, 31: s580-s581. DOI: 10.1016/j.annonc.2020.08.819.Peer-Reviewed Original ResearchUrothelial cancerAdvanced urothelial cancerEfficacy of pembrolizumabKEYNOTE-045KEYNOTE-052PembrolizumabPatientsCancer
2019
902O An adaptive, biomarker directed platform study in metastatic urothelial cancer (BISCAY) with durvalumab in combination with targeted therapies
Powles T, Balar A, Gravis G, Jones R, Ravaud A, Florence J, Grivas P, Petrylak D, Galsky M, Carles J, Sridhar S, Arkenau H, Carroll D, DeCesare J, Mercier F, Hodgson D, Stone J, Cosaert J, Landers D. 902O An adaptive, biomarker directed platform study in metastatic urothelial cancer (BISCAY) with durvalumab in combination with targeted therapies. Annals Of Oncology 2019, 30: v356-v357. DOI: 10.1093/annonc/mdz249.001.Peer-Reviewed Original ResearchSarah Cannon Research InstituteBristol-Myers SquibbGenentech/RocheUrothelial cancerSeattle GeneticsMonotherapy armArm BClovis OncologyRoche LaboratoriesAstellas PharmaNext-generation sequencingRoche-GenentechAdvanced urothelial cancerConclusions Combination treatmentNon-randomized controlsMetastatic urothelial cancerPD-L1 expressionKey secondary objectivePD-L1 inhibitorsTumor DNA alterationsEli LillyBavarian NordicConfirmed responsesD monotherapyOS rates919P Three-year follow-up from the phase III KEYNOTE-045 trial: Pembrolizumab (Pembro) versus investigator’s choice (paclitaxel, docetaxel, or vinflunine) in recurrent, advanced urothelial cancer (UC)
Necchi A, Fradet Y, Bellmunt J, de Wit R, Lee J, Fong L, Vozelgang N, Climent M, Petrylak D, Choueiri T, Gerritsen W, Gurney H, Quinn D, Culine S, Sternberg C, Nam K, Frenkl T, Godwin J, Bajorin D, Vaughn D. 919P Three-year follow-up from the phase III KEYNOTE-045 trial: Pembrolizumab (Pembro) versus investigator’s choice (paclitaxel, docetaxel, or vinflunine) in recurrent, advanced urothelial cancer (UC). Annals Of Oncology 2019, 30: v366-v367. DOI: 10.1093/annonc/mdz249.018.Peer-Reviewed Original ResearchGenentech/RocheDuration of responseCaris Life SciencesBristol-Myers SquibbMetastatic urothelial cancerSubsidiary of MerckUrothelial cancerDohme Corp.US OncologyMerck SharpAdverse eventsRoche LaboratoriesJanssen-CilagInvestigator's choiceKey secondary end pointMedian DORTreatment-related adverse eventsSeattle GeneticsAdvanced urothelial cancerECOG PS 0Kidney Cancer AssociationPlatinum-containing regimenSecondary end pointsAstellas PharmaCancer Study GroupTROPHY-U-01: A phase II open-label study of sacituzumab govitecan (IMMU-132) in patients with advanced urothelial cancer after progression on platinum-based chemotherapy and/or anti-PD-1/PD-L1 checkpoint inhibitor therapy.
Tagawa S, Petrylak D, Grivas P, Agarwal N, Sternberg C, Hernandez C, Siemon-Hryczyk P, Goswami T, Loriot Y. TROPHY-U-01: A phase II open-label study of sacituzumab govitecan (IMMU-132) in patients with advanced urothelial cancer after progression on platinum-based chemotherapy and/or anti-PD-1/PD-L1 checkpoint inhibitor therapy. Journal Of Clinical Oncology 2019, 37: tps3153-tps3153. DOI: 10.1200/jco.2019.37.15_suppl.tps3153.Peer-Reviewed Original ResearchObjective response rateAdvanced urothelial cancerProgression-free survivalCheckpoint inhibitor therapyPhase 2 trialSacituzumab govitecanUrothelial cancerEvaluable ptsAdverse eventsInhibitor therapyEastern Cooperative Oncology Group performance status scorePhase II open-label studyTrop-2Median progression-free survivalNeutropenia/neutrophil countEpithelial cell surface antigenOpen-label studyPerformance status scorePhase 1/2 trialPlatinum-based chemotherapyActive metabolite SN38Cell surface antigensFebrile neutropeniaMeasurable diseasePivotal cohortTROPHY-u-01: A phase II open-label study of sacituzumab govitecan (IMMU-132) in patients with advanced urothelial cancer after progression on platinum-based chemotherapy and/or anti-PD-1/PD-L1 checkpoint inhibitor therapy.
Tagawa S, Petrylak D, Grivas P, Agarwal N, Sternberg C, Siemon-Hryczyk P, Goswam T, Loriot Y. TROPHY-u-01: A phase II open-label study of sacituzumab govitecan (IMMU-132) in patients with advanced urothelial cancer after progression on platinum-based chemotherapy and/or anti-PD-1/PD-L1 checkpoint inhibitor therapy. Journal Of Clinical Oncology 2019, 37: tps495-tps495. DOI: 10.1200/jco.2019.37.7_suppl.tps495.Peer-Reviewed Original ResearchObjective response rateMetastatic urothelial cancerPlatinum-based chemotherapyCheckpoint inhibitor therapyPhase 2 trialSacituzumab govitecanAdverse eventsInhibitor therapyUrothelial cancerPhase II open-label studyTrop-2Median progression-free survivalAdvanced urothelial cancerEpithelial cell surface antigenMedian overall survivalOpen-label studySafety/tolerabilityProgression-free survivalSingle-arm trialCell surface antigensAdvanced UCEvaluable ptsPrior therapyRECIST 1.1Overall survival
2018
901P Impact of prognostic factors and risk groups on overall survival (OS) in patients treated with pembrolizumab vs investigator’s choice chemotherapy for advanced urothelial cancer (UC): Post hoc analysis of KEYNOTE-045
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, Jensen E, Frenkl T, Perini R, Bajorin D. 901P Impact of prognostic factors and risk groups on overall survival (OS) in patients treated with pembrolizumab vs investigator’s choice chemotherapy for advanced urothelial cancer (UC): Post hoc analysis of KEYNOTE-045. Annals Of Oncology 2018, 29: viii320-viii321. DOI: 10.1093/annonc/mdy283.110.Peer-Reviewed Original ResearchPembrolizumab (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
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 metastasesHealth-related quality of life (HRQoL) of pembrolizumab (pembro) vs chemotherapy (chemo) for previously treated advanced urothelial cancer (UC) in KEYNOTE-045.
De Wit R, Bajorin D, Bellmunt J, 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, Li H, Perini R, Vaughn D. Health-related quality of life (HRQoL) of pembrolizumab (pembro) vs chemotherapy (chemo) for previously treated advanced urothelial cancer (UC) in KEYNOTE-045. Journal Of Clinical Oncology 2017, 35: 4530-4530. DOI: 10.1200/jco.2017.35.15_suppl.4530.Peer-Reviewed Original ResearchAdvanced urothelial cancerGlobal health status/QoL scoreUrothelial cancerKEYNOTE-045HRQoL instrumentsQOL scoresWk 15Cox proportional hazards modelStratified log-rank testHRQOL end pointsSecond-line therapyTreatment-related AEsHealth-related qualityLog-rank testProportional hazards modelSuperior OSBetter HRQoLHRQoL analysisStudy treatmentPembroHazards modelInvestigator's choiceRate of improvementLongitudinal data analysis modelEnd pointHealth-related quality of life (HRQoL) in the KEYNOTE-045 study of pembrolizumab versus investigator-choice chemotherapy for previously treated advanced urothelial cancer.
Vaughn D, Bellmunt J, De Wit R, 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, Li H, Perini R, Bajorin D. Health-related quality of life (HRQoL) in the KEYNOTE-045 study of pembrolizumab versus investigator-choice chemotherapy for previously treated advanced urothelial cancer. Journal Of Clinical Oncology 2017, 35: 282-282. DOI: 10.1200/jco.2017.35.6_suppl.282.Peer-Reviewed Original ResearchGlobal health status/QoL scoreAdvanced UCKEYNOTE-045HRQoL instrumentsQOL scoresWk 15Cox proportional hazards modelStratified log-rank testAdvanced urothelial cancerHRQOL end pointsInvestigator-choice chemotherapySecond-line therapyTreatment-related AEsHealth-related qualityLog-rank testProportional hazards modelSuperior OSBetter HRQoLHRQoL analysisUrothelial cancerStudy treatmentPembroHazards modelInvestigator's choiceRate of improvement3LBA Pembrolizumab vs investigator-choice chemotherapy for previously treated advanced urothelial cancer: Phase 3 KEYNOTE-045 study
Necchi A, Bellmunt J, De Wit R, Vaughn D, Fradet Y, Lee J, Fong L, Vogelzang N, Climent M, Petrylak D, Choueiri T, Gerritsen W, Gurney H, Quinn D, Culine S, Sternberg C, Mai Y, Puhlmann M, Perini R, Bajorin D. 3LBA Pembrolizumab vs investigator-choice chemotherapy for previously treated advanced urothelial cancer: Phase 3 KEYNOTE-045 study. European Journal Of Cancer 2017, 72: s2. DOI: 10.1016/s0959-8049(17)30092-8.Peer-Reviewed Original ResearchAdvanced urothelial cancerInvestigator-choice chemotherapyUrothelial cancerPembrolizumabChemotherapyCancer
2016
842TiP A multicentre, international, randomised, open-label phase 3 trial of avelumab + best supportive care (BSC) vs BSC alone as maintenance therapy after first-line platinum-based chemotherapy in patients with advanced urothelial cancer (JAVELIN bladder 100)
Powles T, Grivas P, Aragon-Ching J, Faroun Y, Kessler E, Tomita Y, Chakrabarti D, Laliberte R, Shnaidman M, Petrylak D. 842TiP A multicentre, international, randomised, open-label phase 3 trial of avelumab + best supportive care (BSC) vs BSC alone as maintenance therapy after first-line platinum-based chemotherapy in patients with advanced urothelial cancer (JAVELIN bladder 100). Annals Of Oncology 2016, 27: vi292. DOI: 10.1093/annonc/mdw373.69.Peer-Reviewed Original Research