2024
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.
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 patients
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 populationA phase 2 expansion study of ARV-766, a PROTAC androgen receptor (AR) degrader, in metastatic castration-resistant prostate cancer (mCRPC).
Petrylak D, Stewart T, Gao X, Berghorn E, Lu H, Chan E, Gedrich R, Lang J, McKean M. A phase 2 expansion study of ARV-766, a PROTAC androgen receptor (AR) degrader, in metastatic castration-resistant prostate cancer (mCRPC). Journal Of Clinical Oncology 2023, 41: tps290-tps290. DOI: 10.1200/jco.2023.41.6_suppl.tps290.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerNovel hormonal agentsCohort expansionDisease progressionEastern Cooperative Oncology Group performance status scoreOngoing androgen deprivation therapyProstate-specific antigen (PSA) declineCastration-resistant prostate cancerGonadotropin-releasing hormone analogueCohort expansion studyAndrogen deprivation therapyPerformance status scoreOverall response ratePhase 1 portionWild-type ARDeprivation therapyPrior chemotherapyCurative optionDose escalationAvailable therapiesHormonal agentsStatus scoreCurrent therapiesLigand-binding domainClinical trials
2022
Phase 1/2 study of ARV-110, an androgen receptor (AR) PROTAC degrader, in metastatic castration-resistant prostate cancer (mCRPC).
Gao X, Burris H, Vuky J, Dreicer R, Sartor A, Sternberg C, Percent I, Hussain M, Kalebasty A, Shen J, Heath E, Abesada-Terk G, Gandhi S, McKean M, Lu H, Berghorn E, Gedrich R, Chirnomas S, Vogelzang N, Petrylak D. Phase 1/2 study of ARV-110, an androgen receptor (AR) PROTAC degrader, in metastatic castration-resistant prostate cancer (mCRPC). Journal Of Clinical Oncology 2022, 40: 17-17. DOI: 10.1200/jco.2022.40.6_suppl.017.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerNovel hormonal agentsProstate-specific antigenClinical activityBetter prostate-specific antigenOngoing phase 1/2 studyCastration-resistant prostate cancerBiomarker-defined subgroupsPhase 2 dosePhase 1/2 studyWild-type ARFourth subgroupPhase 1AR alterationsRECIST responseSpecific molecular profilePrior therapyAdverse eventsAR-V7Tumor shrinkageHormonal agentsTreatment optionsClinical historyDisease progressionProstate cancerImpact of primary tumor location on efficacy and safety of pembrolizumab (pembro) in patients (pts) with locally advanced or metastatic urothelial carcinoma (UC) enrolled in the phase 2 KEYNOTE-052 and phase 3 KEYNOTE-045 trials.
O'Donnell P, Balar A, Castellano D, De Wit R, Vaughn D, Powles T, Vuky J, Lee J, Fradet Y, Bellmunt J, Fong L, Petrylak D, Gerritsen W, Quinn D, Culine S, Bajorin D, Xu J, Imai K, Moreno B, Grivas P. Impact of primary tumor location on efficacy and safety of pembrolizumab (pembro) in patients (pts) with locally advanced or metastatic urothelial carcinoma (UC) enrolled in the phase 2 KEYNOTE-052 and phase 3 KEYNOTE-045 trials. Journal Of Clinical Oncology 2022, 40: 516-516. DOI: 10.1200/jco.2022.40.6_suppl.516.Peer-Reviewed Original ResearchMetastatic urothelial carcinomaPrimary tumor locationKEYNOTE-045KEYNOTE-052Urothelial carcinomaTumor locationRECIST v1.1Primary tumorSafety of pembrolizumabSimilar clinical activityWithdrawal of consentMeasurable diseaseData cutoffManageable safetyUnacceptable toxicitySystemic therapyPD-L1Positive tumorsRenal pelvisDisease progressionPembroSimilar efficacyClinical activityGrade 3UT group
2020
343 Phase 3 study of pembrolizumab + docetaxel and prednisone/prednisolone for metastatic castration-resistant prostate cancer (mCRPC) pretreated with next-generation hormonal agents (NHAs) (KEYNOTE-921)
Petrylak D, Shore N, Bennamoun M, Ratta R, Piulats J, Li B, Schloss C, Fizazi K. 343 Phase 3 study of pembrolizumab + docetaxel and prednisone/prednisolone for metastatic castration-resistant prostate cancer (mCRPC) pretreated with next-generation hormonal agents (NHAs) (KEYNOTE-921). Journal For ImmunoTherapy Of Cancer 2020, 8: a209-a210. DOI: 10.1136/jitc-2020-sitc2020.0343.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerNext-generation hormonal agentsPrednisone/prednisoloneProgression-free survivalObjective response rateDuration of responseSecondary end pointsOverall survivalDisease progressionResponse ratePrior treatmentRECIST v1.1End pointAbiraterone acetateEastern Cooperative Oncology Group performance status 0/1Prostate-specific antigen (PSA) response rateDual primary end pointsKey secondary end pointRadiographic progression-free survivalCastration-resistant prostate cancerPerformance status 0/1PSA response rateSubsequent anticancer therapyAndrogen deprivation therapyPrimary end pointRelationship between hyperphosphatemia with infigratinib (BGJ398) and efficacy in FGFR3 -altered advanced/metastatic urothelial carcinoma (aUC).
Lyou Y, Grivas P, Rosenberg J, Hoffman-Censits J, Quinn D, Petrylak D, Galsky M, Vaishampayan U, De Giorgi U, Gupta S, Burris H, Rearden J, Ye Y, Wang H, Moran S, Daneshmand S, Bajorin D, Pal S. Relationship between hyperphosphatemia with infigratinib (BGJ398) and efficacy in FGFR3 -altered advanced/metastatic urothelial carcinoma (aUC). Journal Of Clinical Oncology 2020, 38: 576-576. DOI: 10.1200/jco.2020.38.6_suppl.576.Peer-Reviewed Original ResearchDisease control rateOverall response rateTreatment lengthFGFR inhibitorsPrior platinum-based chemotherapyClass effectMedian treatment lengthRECIST 1.0 criteriaCommon adverse eventsMetastatic urothelial carcinomaSignificant clinical activityPlatinum-based chemotherapyPhosphate binder sevelamerMutations/fusionsEligible patientsEfficacy outcomesUnacceptable toxicityAdverse eventsFGFR3 alterationsEfficacy findingsUrothelial carcinomaControl ratePharmacodynamic biomarkersDisease progressionClinical activityAnalysis of clinical outcomes according to response status in prospective clinical trials of atezolizumab (atezo) in pretreated locally advanced/metastatic urothelial carcinoma (mUC).
Bedke J, Merseburger A, Loriot Y, Castellano D, Choy E, Duran I, Rosenberg J, Petrylak D, Dreicer R, Perez-Gracia J, Hoffman-Censits J, Van Der Heijden M, Degaonkar V, Thiebach L, de Ducla S, Fear S, Powles T, Sternberg C. Analysis of clinical outcomes according to response status in prospective clinical trials of atezolizumab (atezo) in pretreated locally advanced/metastatic urothelial carcinoma (mUC). Journal Of Clinical Oncology 2020, 38: 492-492. DOI: 10.1200/jco.2020.38.6_suppl.492.Peer-Reviewed Original ResearchMetastatic urothelial carcinomaStable diseasePartial responseDisease controlBaseline characteristicsRisk factorsPR/stable diseaseOverall survival durationProspective clinical trialsBroader patient populationAnalysis of outcomesData cutoffUnacceptable toxicityWorse OSComplete responseClinical outcomesMedian timeAnalysis populationPatient populationUrothelial carcinomaSurvival durationClinical trialsCohort 2Disease progressionResponse status
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 endpointEV-103: Enfortumab vedotin plus pembrolizumab and/or chemotherapy for locally advanced or metastatic urothelial cancer.
Hoimes C, Rosenberg J, Petrylak D, Carret A, Melhem-Bertrandt A, Flaig T. EV-103: Enfortumab vedotin plus pembrolizumab and/or chemotherapy for locally advanced or metastatic urothelial cancer. Journal Of Clinical Oncology 2019, 37: tps4593-tps4593. DOI: 10.1200/jco.2019.37.15_suppl.tps4593.Peer-Reviewed Original ResearchMetastatic urothelial cancerCheckpoint inhibitorsDay 1Urothelial cancerCombination therapyMicrotubule-disrupting agent monomethyl auristatin EInvestigational antibody-drug conjugateFirst-line cisplatinPlatinum-containing regimenDisease control rateImmune checkpoint inhibitorsPhase 1b trialPhase 1 studyDuration of responseEnhanced immune responseMonomethyl auristatin EAntibody-drug conjugatesDose expansionResponse durabilityControl rateDisease progressionImmune responseAuristatin EResponse rateNectin-4EV-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
Overall survival and immune responses with sipuleucel-T and enzalutamide: STRIDE study.
Petrylak D, Drake C, Pieczonka C, Corman J, Garcia J, Dunshee C, Van Mouwerik T, Tyler R, Chang N, Quinn D. Overall survival and immune responses with sipuleucel-T and enzalutamide: STRIDE study. Journal Of Clinical Oncology 2018, 36: 246-246. DOI: 10.1200/jco.2018.36.6_suppl.246.Peer-Reviewed Original ResearchDisease progressionMetastatic castration-resistant prostate cancerCastration-resistant prostate cancerKaplan-Meier analysisNew safety concernsMedian followBaseline characteristicsOverall survivalPSA responseMedian ageClinical outcomesHormonal agentsProstate cancerClinical impactLaboratory valuesSTRIDE studyImmune responseLarger studySipuleucelWkSafety concernsFirst studyImmunotherapyPatientsFollowEnfortumab 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 endpoint
2015
Interim results of a randomized phase 2 study of docetaxel with ramucirumab versus docetaxel in second-line advanced or metastatic urothelial carcinoma.
Petrylak D, Tagawa S, Kohli M, Tang S, Zhang H, Hamid O, Kauh J, Walgren R, Chi K. Interim results of a randomized phase 2 study of docetaxel with ramucirumab versus docetaxel in second-line advanced or metastatic urothelial carcinoma. Journal Of Clinical Oncology 2015, 33: 295-295. DOI: 10.1200/jco.2015.33.7_suppl.295.Peer-Reviewed Original ResearchRandomized phase 2 studyMetastatic urothelial carcinomaPhase 2 studyUrothelial carcinomaDisease progressionInterim analysisMetastatic platinum-resistant urothelial carcinomaDisease control rateECOG PS 0ECOG PS 1Investigator-assessed PFSAdvanced urothelial carcinomaCommon adverse eventsFirst-line chemotherapyMedian PFSPlatinum regimenRECIST v1.1Febrile neutropeniaPrimary endpointVisceral metastasesPFS eventsPS 0Unacceptable toxicityAdverse eventsStudy arms
2012
A phase III, randomized, double-blind, multicenter trial comparing the investigational agent orteronel (TAK-700) plus prednisone (P) with placebo plus P in patients with metastatic castration-resistant prostate cancer (mCRPC) that has progressed during or following docetaxel-based therapy.
Dreicer R, Agus D, Bellmunt J, De Bono J, Petrylak D, Tejura B, Shi Y, Fizazi K. A phase III, randomized, double-blind, multicenter trial comparing the investigational agent orteronel (TAK-700) plus prednisone (P) with placebo plus P in patients with metastatic castration-resistant prostate cancer (mCRPC) that has progressed during or following docetaxel-based therapy. Journal Of Clinical Oncology 2012, 30: tps4693-tps4693. DOI: 10.1200/jco.2012.30.15_suppl.tps4693.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerDisease progressionRadiographic progression-free survivalProstate-specific antigen levelCastration-resistant prostate cancerChemotherapy-naïve menDocetaxel-based therapyPhase 1/2 studyPhase 3 studyProgression-free survivalPatient-reported outcomesNew therapeutic optionsTestosterone synthesis pathwayERG fusion geneBone painMedical castrationNoncurative therapyHormonal therapyPrimary endpointPSA decreasePSA progressionStudy drugMetastatic diseaseObjective responseOverall survival
2010
Docetaxel
Phillips C, Petrylak D. Docetaxel. 2010, 133-146. DOI: 10.1007/978-1-60327-829-4_12.Peer-Reviewed Original ResearchCastration-resistant prostate cancerAndrogen deprivation therapyProstate-specific antigenProstate cancerInitial androgen deprivation therapyFirst treatment regimenSecondary hormonal manipulationsStandard chemotherapy combinationTaxane combination therapyFirst-line treatmentUse of docetaxelProstate cancer screeningDeprivation therapyRecurrent diseaseChemotherapy combinationsDocetaxel therapyPSA responseTreatment regimenTreatment optionsCancer screeningDisease progressionHormonal manipulationBetter survivalInvestigational usesSurgical castration
2006
Clinical benefit of atrasentan for men with metastatic hormone-refractory prostate cancer metastatic to bone
Sleep D, Nelson J, Petrylak D, Isaacson J, Carducci M. Clinical benefit of atrasentan for men with metastatic hormone-refractory prostate cancer metastatic to bone. Journal Of Clinical Oncology 2006, 24: 4630-4630. DOI: 10.1200/jco.2006.24.18_suppl.4630.Peer-Reviewed Original ResearchHormone-refractory prostate cancerDisease progressionHRPC patientsBone metastasesProstate cancer metastaticKaplan-Meier methodDelays disease progressionEffects of endothelinDisease progression eventsCox proportional hazardsProgression of morbidityBone painCancer metastaticRadiographic progressionProlong survivalClinical benefitClinical progressionSelective endothelinClinical eventsReceptor antagonistMultinational trialProstate cancerClinical meansAtrasentanNew therapies
2000
A Phase II Pilot Study of KW-2189 in Patients with Advanced Renal Cell Carcinoma
Small E, Figlin R, Petrylak D, Vaughn D, Sartor O, Horak I, Pincus R, Kremer A, Bowden C. A Phase II Pilot Study of KW-2189 in Patients with Advanced Renal Cell Carcinoma. Investigational New Drugs 2000, 18: 193-198. PMID: 10857997, DOI: 10.1023/a:1006386115312.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaMetastatic renal cell carcinomaCell carcinomaOpen-label phase II trialCommon drug-related toxicitiesAdvanced renal cell carcinomaPhase II pilot studyNon-hematologic toxicitiesPhase II trialDrug-related toxicityPredictable safety profileReversible myelosuppressionII trialObjective responseSafety profileDisease progressionModerate fatigueWeek 6PatientsSignificant toxicityCarcinomaPilot studyAntitumor potencyWater-soluble analogueCycle 1Androgen deprivation and four courses of fixed-schedule suramin treatment in patients with newly diagnosed metastatic prostate cancer: A Southwest Oncology Group Study.
Hussain M, Fisher E, Petrylak D, O’Connor J, Wood D, Small E, Eisenberger M, Crawford E. Androgen deprivation and four courses of fixed-schedule suramin treatment in patients with newly diagnosed metastatic prostate cancer: A Southwest Oncology Group Study. Journal Of Clinical Oncology 2000, 18: 1043-9. PMID: 10694555, DOI: 10.1200/jco.2000.18.5.1043.Peer-Reviewed Original ResearchConceptsMetastatic prostate cancerAndrogen deprivationProstate cancerTreatment interruptionGrade 3Southwest Oncology Group studyCombination of suraminTherapy-related deathsGrade 4 toxicityCooperative group settingTreatment of patientsNumber of patientsFeasibility of treatmentAdequate hematologicOverall survivalCoagulation parametersDisease progressionSuramin treatmentPatientsSecond courseTreatment cyclesMultiple coursesCancerSuraminSuch treatment