2024
Trastuzumab Deruxtecan With Nivolumab in HER2-Expressing Metastatic Breast or Urothelial Cancer: Analysis of the Phase Ib DS8201-A-U105 Study
Hamilton E, Galsky M, Ochsenreither S, Del Conte G, Martín M, de Miguel M, Yu E, Williams A, Gion M, Tan A, Agrawal L, Rutten A, Machiels J, Cresta S, Debruyne P, Hennequin A, Moreno V, Minchom A, Valdes-Albini F, Petrylak D, Li L, Tsuchihashi Z, Suto F, Cheng F, Kandil M, Barrios D, Hurvitz S. Trastuzumab Deruxtecan With Nivolumab in HER2-Expressing Metastatic Breast or Urothelial Cancer: Analysis of the Phase Ib DS8201-A-U105 Study. Clinical Cancer Research 2024 PMID: 39405343, DOI: 10.1158/1078-0432.ccr-24-1513.Peer-Reviewed Original ResearchMetastatic urothelial cancerMetastatic breast cancerT-DXdHER2-lowTrastuzumab deruxtecanUrothelial cancerHER2-positive metastatic breast cancerCohort 1Treatment-emergent adverse eventsMedian treatment durationIndependent central reviewData cutoffMetastatic breastCentral reviewPrimary endpointNivolumabCohort 4Adverse eventsBreast cancerCohort 3Cohort 2Evaluate efficacyTreatment durationPrompt interventionPatients1622P A phase II study of the first-in-class oral innate immune activator BXCL701 with pembrolizumab in patients with metastatic castration-resistant prostate cancer (mCRPC): Long-term follow-up
Aggarwal R, Tagawa S, Monk P, Zhu X, Jones R, Linch M, Costin D, de Bono J, Karsh L, Petrylak D, Borderies P, Deshpande R, O'Neill V, Zhang J. 1622P A phase II study of the first-in-class oral innate immune activator BXCL701 with pembrolizumab in patients with metastatic castration-resistant prostate cancer (mCRPC): Long-term follow-up. Annals Of Oncology 2024, 35: s979. DOI: 10.1016/j.annonc.2024.08.1703.Peer-Reviewed Original Research1968P 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 ResearchImpact of Prior Chemotherapy on Response to Second-line Pembrolizumab in Urothelial Cancer: Exploratory Analysis of the Phase 3 KEYNOTE-045 Trial
de Wit R, Vaughn D, Fradet Y, Fong L, Climent M, Necchi A, Petrylak D, Gerritsen W, Gurney H, Quinn D, Culine S, Sternberg C, Bajorin D, Choueiri T, Xu J, Imai K, Homet Moreno B, Bellmunt J, Lee J. Impact of Prior Chemotherapy on Response to Second-line Pembrolizumab in Urothelial Cancer: Exploratory Analysis of the Phase 3 KEYNOTE-045 Trial. European Urology 2024 PMID: 39174409, DOI: 10.1016/j.eururo.2024.07.015.Peer-Reviewed Original ResearchPlatinum-based chemotherapyDuration of responseFirst-line platinum-based chemotherapySecond-line pembrolizumabUrothelial carcinomaProgressive diseaseOverall survivalResponse to first-line platinum-based chemotherapyMedian duration of responsePlatinum-based combination chemotherapyStandard first-line treatmentStandard-of-care treatmentAdvanced urothelial carcinomaAvelumab maintenance therapyResponse to pembrolizumabSolid Tumors versionResponse Evaluation CriteriaEfficacy of pembrolizumabSecond-line treatmentFirst-line treatmentPost hoc analysisAdvanced UCMedian OSPembrolizumab monotherapyPrior chemotherapyPatient-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 4Sacituzumab 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 expressionARV-766, a proteolysis targeting chimera (PROTAC) androgen receptor (AR) degrader, in metastatic castration-resistant prostate cancer (mCRPC): Initial results of a phase 1/2 study.
Petrylak D, McKean M, Lang J, Gao X, Dreicer R, Geynisman D, Stewart T, Gandhi M, Appleman L, Dorff T, Chatta G, Tutrone R, De La Cerda J, Berghorn E, Gong J, Yu T, Dominy E, Chan E, Shore N. ARV-766, a proteolysis targeting chimera (PROTAC) androgen receptor (AR) degrader, in metastatic castration-resistant prostate cancer (mCRPC): Initial results of a phase 1/2 study. Journal Of Clinical Oncology 2024, 42: 5011-5011. DOI: 10.1200/jco.2024.42.16_suppl.5011.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerTreatment-related adverse eventsAR-LBD mutationsPhase 1/2 studyClinical activityProstate cancerAndrogen receptorAdverse eventsMetastatic castration-resistant prostate cancer treatmentProgressive metastatic castration-resistant prostate cancerPhase 1 dose-escalation portionDisease progressionTreatment-emergent adverse eventsCastration-resistant prostate cancerResistant to available therapiesAssociated with poor outcomesDose-limiting toxicityAndrogen deprivation therapyAdvanced prostate cancerIncreased blood creatinineWild-type ARSubgroup of patientsDose-dependent increaseDeprivation therapyPretreated patientsA 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 responseAvelumab first-line maintenance (1LM) for advanced urothelial carcinoma (aUC): Long-term outcomes from JAVELIN Bladder 100 in patients (pts) with low tumor burden.
Bellmunt J, Powles T, Park S, Voog E, Valderrama B, Gurney H, Ullén A, Loriot Y, Sridhar S, Tsuchiya N, Sternberg C, Aragon-Ching J, Petrylak D, Climent Duran M, Tyroller K, Hoffman J, Jacob N, Grivas P, Gupta S. Avelumab first-line maintenance (1LM) for advanced urothelial carcinoma (aUC): Long-term outcomes from JAVELIN Bladder 100 in patients (pts) with low tumor burden. Journal Of Clinical Oncology 2024, 42: 4566-4566. DOI: 10.1200/jco.2024.42.16_suppl.4566.Peer-Reviewed Original ResearchAdvanced urothelial carcinomaLow tumor burdenProgression-free survivalBest supportive carePlatinum-based chemotherapyTreatment-related adverse eventsTumor burdenOverall survivalNonvisceral metastasesPost hoc analysisIncidence of treatment-related adverse eventsPost-hoc analysis of efficacyFirst-line maintenanceImmune checkpoint inhibitorsMedian follow-upProlonged overall survivalAssociated with better outcomesAnalysis of efficacyLong-term outcomesAnticancer drug treatmentJAVELIN BladderLA diseaseNonvisceral diseaseCheckpoint inhibitorsMetastatic UCAvelumab first-line (1L) maintenance for advanced urothelial carcinoma (aUC): Long-term outcomes from the JAVELIN Bladder 100 trial in patients (pts) with histological subtypes.
Loriot Y, Gupta S, Powles T, Grivas P, Petrylak D, Tyroller K, Jacob N, Hoffman J, Bellmunt J. Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (aUC): Long-term outcomes from the JAVELIN Bladder 100 trial in patients (pts) with histological subtypes. Journal Of Clinical Oncology 2024, 42: 4567-4567. DOI: 10.1200/jco.2024.42.16_suppl.4567.Peer-Reviewed Original ResearchAdvanced urothelial carcinomaTreatment-related adverse eventsPlatinum-based chemotherapyProgression-free survivalBSC-alone armHistological subtypesLong-term outcomesOverall survivalPost hoc analysisTreatment guidelinesAnalysis of long-term outcomesStandard-of-care treatmentMedian follow-upOverall populationLong-term efficacyInternational treatment guidelinesLong-term safetyJAVELIN BladderMetastatic UCSafety populationData cutoffEligible ptsUrothelial carcinomaFirst-linePrimary endpointStudy 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 vedotinMP14-19 ARV-766, A PROTAC ANDROGEN RECEPTOR (AR) DEGRADER, COMBINED WITH ABIRATERONE IN NOVEL HORMONAL AGENT (NHA)-NAÏVE METASTATIC PROSTATE CANCER: PHASE 1 COHORT (PART C) OF A PHASE 1/2 STUDY
Shore N, Lang J, Geynisman D, Stewart T, Gao X, Appleman L, Dreicer R, Dorff T, Berghorn E, Duperret E, Lu H, Chan E, Garmezy B, Petrylak D. MP14-19 ARV-766, A PROTAC ANDROGEN RECEPTOR (AR) DEGRADER, COMBINED WITH ABIRATERONE IN NOVEL HORMONAL AGENT (NHA)-NAÏVE METASTATIC PROSTATE CANCER: PHASE 1 COHORT (PART C) OF A PHASE 1/2 STUDY. Journal Of Urology 2024, 211: e227. DOI: 10.1097/01.ju.0001009428.69695.82.19.Peer-Reviewed Original ResearchA Plain Language Summary Exploring a New Treatment Combination for Untreated Locally Advanced or Metastatic Urothelial Cancer: Enfortumab Vedotin Plus Pembrolizumab
Hoimes C, Flaig T, Milowsky M, Friedlander T, Bilen M, Gupta S, Srinivas S, Merchan J, McKay R, Petrylak D, Sasse C, Moreno B, Yu Y, Carret A, Rosenberg J. A Plain Language Summary Exploring a New Treatment Combination for Untreated Locally Advanced or Metastatic Urothelial Cancer: Enfortumab Vedotin Plus Pembrolizumab. Future Oncology 2024, 20: 351-360. PMID: 37994649, PMCID: PMC10988537, DOI: 10.2217/fon-2023-0112.Peer-Reviewed Original ResearchEfficacy 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 MEDLINEAvelumab first-line (1L) maintenance for advanced urothelial carcinoma (aUC): Long-term outcomes from the JAVELIN Bladder 100 trial in patients (pts) with high body mass index (BMI).
Aragon-Ching J, Petrylak D, Sridhar S, Gupta S, Grivas P, Powles T, Gurney H, Jacob N, Tyroller K, Guenther S, Bellmunt J. Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (aUC): Long-term outcomes from the JAVELIN Bladder 100 trial in patients (pts) with high body mass index (BMI). Journal Of Clinical Oncology 2024, 42: 600-600. DOI: 10.1200/jco.2024.42.4_suppl.600.Peer-Reviewed Original ResearchProgression-free survivalAdvanced urothelial carcinomaPlatinum-based chemotherapyBody mass indexHigher body mass indexLong-term outcomesOverall survivalLong-term safetyStandard of careMedian progression-free survivalProgression-free survival ratesAnalysis of long-term outcomesBSC-alone armMedian follow-upProlonged overall survivalLevel 1 evidenceLong-term efficacyInternational treatment guidelinesPost hoc analysisJAVELIN BladderMedian OSMetastatic UCOS ratesSafety populationData cutoffSWOG S2210: A phase II study of neoadjuvant carboplatin for localized, high-risk prostate cancer with germline BRCA1/2 mutations.
Cheng H, Callis S, Lin D, Yu E, Dorff T, Kase A, Tangen C, Petrylak D, Lerner S. SWOG S2210: A phase II study of neoadjuvant carboplatin for localized, high-risk prostate cancer with germline BRCA1/2 mutations. Journal Of Clinical Oncology 2024, 42: tps354-tps354. DOI: 10.1200/jco.2024.42.4_suppl.tps354.Peer-Reviewed Original ResearchPathological complete responseHigh-risk diseaseNeoadjuvant carboplatinRadical prostatectomyProstate cancerComplete responseCarriers of germline pathogenic variantsRate of pathological complete responseHigh-risk prostate cancerGermline BRCA1/2 mutationsPlatinum-based regimensBiochemical recurrence-freeMetastatic prostate cancerPhase II studyCurative intent treatmentGermline genetic testingGermline pathogenic variantsMonitoring of recurrenceFDA-approved optionsLate-stage diseaseGBRCA1/2mRecurrence-freeBRCA1/2 mutationsMetastasis-freeOverall survivalSacituzumab Govitecan in Combination With Pembrolizumab for Patients With Metastatic Urothelial Cancer That Progressed After Platinum-Based Chemotherapy: TROPHY-U-01 Cohort 3
Grivas P, Pouessel D, Park C, Barthelemy P, Bupathi M, Petrylak D, Agarwal N, Gupta S, Fléchon A, Ramamurthy C, Davis N, Recio-Boiles A, Sternberg C, Bhatia A, Pichardo C, Sierecki M, Tonelli J, Zhou H, Tagawa S, Loriot Y. Sacituzumab Govitecan in Combination With Pembrolizumab for Patients With Metastatic Urothelial Cancer That Progressed After Platinum-Based Chemotherapy: TROPHY-U-01 Cohort 3. Journal Of Clinical Oncology 2024, 42: 1415-1425. PMID: 38261969, PMCID: PMC11095901, DOI: 10.1200/jco.22.02835.Peer-Reviewed Original ResearchMetastatic urothelial cancerPlatinum-based chemotherapyClinical benefit rateProgression-free survivalDuration of responseSacituzumab govitecanCheckpoint inhibitorsCohort 3Central reviewUrothelial cancerFirst-line platinum-based chemotherapyOpen-label phase II studyDay 1Median duration of responseMedian progression-free survivalTreatment-related adverse eventsMedian overall survivalMedian follow-upPhase II studySecondary end pointsAntibody-drug conjugatesMetastatic settingOverall survivalStandard therapyII study