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 patientsSWOG 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 survival
2023
1803P Phase I/II study of bavdegalutamide, a PROTAC androgen receptor (AR) degrader in metastatic castration-resistant prostate cancer (mCRPC): Radiographic progression-free survival (rPFS) in patients (pts) with AR ligand-binding domain (LBD) mutations
Petrylak D, Garmezy B, Shen J, Kalebasty A, Sartor O, Dreicer R, Agarwal N, Hussain M, Percent I, Heath E, Gedrich R, Yu T, Healey D, Parameswaran J, Sternberg C, Gao X. 1803P Phase I/II study of bavdegalutamide, a PROTAC androgen receptor (AR) degrader in metastatic castration-resistant prostate cancer (mCRPC): Radiographic progression-free survival (rPFS) in patients (pts) with AR ligand-binding domain (LBD) mutations. Annals Of Oncology 2023, 34: s973-s974. DOI: 10.1016/j.annonc.2023.09.2751.Peer-Reviewed Original ResearchMaster transcription factor reprograming unleashes selective translation promoting castration resistance and immune evasion in lethal prostate cancer.
Santasusagna S, Zhu S, Jawalagatti V, Carceles-Cordon M, Ertel A, Garcia-Longarte S, Song W, Fujiwara N, Li P, Mendizabal I, Petrylak D, Kelly W, Reddy E, Wang L, Schiewer M, Lujambio A, Karnes J, Knudsen K, Cordon-Cardo C, Dong H, Huang H, Carracedo A, Hoshida Y, Rodriguez-Bravo V, Domingo-Domenech J. Master transcription factor reprograming unleashes selective translation promoting castration resistance and immune evasion in lethal prostate cancer. Cancer Discovery 2023, 13: 2584-2609. PMID: 37676710, PMCID: PMC10714140, DOI: 10.1158/2159-8290.cd-23-0306.Peer-Reviewed Original ResearchConceptsLethal prostate cancerProstate cancerCastration resistanceImmune evasionPharmacologic targetingAnti-PD-1 therapyMajor histocompatibility complex IDeprivation therapyMicrophthalmia transcription factorAndrogen receptorPreclinical modelsTherapeutic strategiesCancerTherapyDruggable mechanismMaster transcription factorTranscription factorsKey mRNAsSpecific mRNAsMRNAFactor 3bEvasionSelected ArticlesTargetingTumorsThe Efficacy of Enzalutamide plus Androgen Deprivation Therapy in Oligometastatic Hormone-sensitive Prostate Cancer: A Post Hoc Analysis of ARCHES
Armstrong A, Iguchi T, Azad A, Villers A, Alekseev B, Petrylak D, Szmulewitz R, Alcaraz A, Shore N, Holzbeierlein J, Gomez-Veiga F, Rosbrook B, Zohren F, Haas G, Gourgiotti G, El-Chaar N, Stenzl A. The Efficacy of Enzalutamide plus Androgen Deprivation Therapy in Oligometastatic Hormone-sensitive Prostate Cancer: A Post Hoc Analysis of ARCHES. European Urology 2023, 84: 229-241. PMID: 37179240, DOI: 10.1016/j.eururo.2023.04.002.Peer-Reviewed Original ResearchConceptsHormone-sensitive prostate cancerAndrogen deprivation therapyRadiographic progression-free survivalMetastatic hormone-sensitive prostate cancerOligometastatic hormone-sensitive prostate cancerOverall survivalProstate cancerDeprivation therapyHazard ratioAndrogen receptor inhibitionEarly treatment intensificationEfficacy of enzalutamideRisk of undertreatmentSystemic treatment strategiesSecondary efficacy endpointsPhase 3 studyProgression-free survivalNumber of metastasesConfidence intervalsProportional hazards modelPost Hoc AnalysisEfficacy endpointOligometastatic diseaseSecondary endpointsTreatment intensificationCombination Treatment with Sipuleucel-T and Abiraterone Acetate or Enzalutamide for Metastatic Castration-Resistant Prostate Cancer: STAMP and STRIDE Trials
Antonarakis E, Subudhi S, Pieczonka C, Karsh L, Quinn D, Hafron J, Wilfehrt H, Harmon M, Sheikh N, Shore N, Petrylak D. Combination Treatment with Sipuleucel-T and Abiraterone Acetate or Enzalutamide for Metastatic Castration-Resistant Prostate Cancer: STAMP and STRIDE Trials. Clinical Cancer Research 2023, 29: 2426-2434. PMID: 37058234, PMCID: PMC10320463, DOI: 10.1158/1078-0432.ccr-22-3832.Peer-Reviewed Original ResearchConceptsMetastatic castration-resistant prostate cancerAndrogen receptor-targeted agentsMedian overall survivalCastration-resistant prostate cancerOverall survivalNational Death IndexConcurrent administrationProstate cancerAntigen-presenting cell activationCurrent prescribing informationNew safety signalsKaplan-Meier methodologyLong-term outcomesConfidence intervalsReceptor-targeted agentsProstatic acid phosphataseAbiraterone acetateFirst infusionDeath IndexPrescribing informationHumoral responseSubsequent infusionSequential administrationSafety signalsImmune responseExternal Validation of a Prognostic Model of Overall Survival in Men With Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer
Halabi S, Yang Q, Roy A, Luo B, Araujo J, Logothetis C, Sternberg C, Armstrong A, Carducci M, N. K, de Bono J, Petrylak D, Fizazi K, Higano C, Morris M, Rathkopf D, Saad F, Ryan C, Small E, Kelly W. External Validation of a Prognostic Model of Overall Survival in Men With Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer. Journal Of Clinical Oncology 2023, 41: 2736-2746. PMID: 37040594, PMCID: PMC10414709, DOI: 10.1200/jco.22.02661.Peer-Reviewed Original ResearchConceptsOverall survivalPrognostic modelPrognostic groupsRisk groupsProstate cancerChemotherapy-Naïve Metastatic CastrationLow-risk prognostic groupsCastration-resistant prostate cancerPrognostic risk groupingsIntermediate-risk groupMedian overall survivalPhase III trialsGroup of patientsPrognostic risk groupsResistant prostate cancerRandomized clinical trialsTime-dependent areaDifferent treatment classesIII trialsInhibitor trialsRisk groupingClinical trialsTreatment subgroupsSpecific subgroupsTrial statusFirst-in-human, phase 1 study of PF-06753512, a vaccine-based immunotherapy regimen (VBIR), in non-metastatic hormone-sensitive biochemical recurrence and metastatic castration-resistant prostate cancer (mCRPC)
Autio K, Higano C, Nordquist L, Appleman L, Zhang T, Zhu X, Babiker H, Vogelzang N, Prasad S, Schweizer M, Madan R, Billotte S, Cavazos N, Bogg O, Li R, Chan K, Cho H, Kaneda M, Wang I, Zheng J, Tang S, Hollingsworth R, Kern K, Petrylak D. First-in-human, phase 1 study of PF-06753512, a vaccine-based immunotherapy regimen (VBIR), in non-metastatic hormone-sensitive biochemical recurrence and metastatic castration-resistant prostate cancer (mCRPC). Journal For ImmunoTherapy Of Cancer 2023, 11: e005702. PMID: 36948505, PMCID: PMC10040068, DOI: 10.1136/jitc-2022-005702.Peer-Reviewed Original ResearchConceptsMetastatic castration-resistant prostate cancerAndrogen deprivation therapyRadiographic progression-free survivalCastration-resistant prostate cancerPhase 1 studyBiochemical recurrenceProstate cancerImmunotherapy regimenMedian durationDose escalationMedian radiographic progression-free survivalAntigen-specific T cell responsesImmune-related adverse eventsRecommended phase 2 doseSpecific T cell responsesPhase 2 doseImmune checkpoint inhibitorsModest antitumor activityObjective response rateProgression-free survivalAntigen-specific immunityT cell responsesInfluenza-like illnessSignificant side effectsDeprivation therapySynthesizing and Applying Molecular Targeted Imaging Results in Patients With Prostate Cancer (RADAR VII)
Crawford E, Harris R, Slovin S, Concepcion R, Albala D, Gomella L, Orio P, Sellinger S, Petrylak D, Koo P. Synthesizing and Applying Molecular Targeted Imaging Results in Patients With Prostate Cancer (RADAR VII). JU Open Plus 2023, 1 DOI: 10.1097/ju9.00000000000000011.Peer-Reviewed Original ResearchProstate cancerNonmetastatic castrate-resistant prostate cancerClinical decisionCastrate-resistant prostate cancerConventional imagingLimited clinical dataTreatment of patientsFuture clinical trialsTreatment decision makingProstate cancer researchLimited available evidenceNuclear medicine specialistsLocalized diseaseMetastatic diseaseMedical oncologistsProspective studyBiochemical recurrenceClinical trialsRadiographic assessmentClinical dataMore robust recommendationsMedicine specialistsClinical experienceConsensus guidanceRadiation oncologists
2022
1398P Overall survival (OS) in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC) who received prior androgen deprivation therapy (ADT) and reached low prostate-specific antigen (PSA) levels treated further with enzalutamide (ENZA): Post hoc analyses of ARCHES
Petrylak D, Azad A, Szmulewitz R, Iguchi T, Shore N, Holzbeierlein J, Alekseev B, El-Chaar N, Rosbrook B, Ma J, Zohren F, Haas G, Stenzl A, Armstrong A. 1398P Overall survival (OS) in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC) who received prior androgen deprivation therapy (ADT) and reached low prostate-specific antigen (PSA) levels treated further with enzalutamide (ENZA): Post hoc analyses of ARCHES. Annals Of Oncology 2022, 33: s1183-s1184. DOI: 10.1016/j.annonc.2022.07.1884.Peer-Reviewed Original ResearchMetastatic hormone-sensitive prostate cancerAndrogen deprivation therapyOverall survivalLow prostate-specific antigen levelsHormone-sensitive prostate cancerPrior androgen deprivation therapyProstate-specific antigen levelDeprivation therapyAntigen levelsProstate cancerEnzalutamidePatientsTherapyCancerEffect of androgen receptor directed therapy in prostate cancer patients with COVID-19.
Unlu S, Shin J, Par-Young J, Vinetz J, Petrylak D, Kang I, Kim J. Effect of androgen receptor directed therapy in prostate cancer patients with COVID-19. Journal Of Clinical Oncology 2022, 40: 161-161. DOI: 10.1200/jco.2022.40.6_suppl.161.Peer-Reviewed Original ResearchProstate cancerPCa patientsAndrogen receptorCOVID-19Mortality rateYale New Haven Health SystemProtective rolePrevalence of PCaRate of hospitalRetrospective chart reviewExpression of TMPRSS2Rate of hospitalizationProstate cancer patientsAndrogen receptor antagonistProstate cancer casesSARS-CoV-2Institutional review boardDirected therapyChart reviewClinical characteristicsGnRH agonistHormone therapyGnRH antagonistHome medicationsClinical outcomesPhase 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 cancerBXCL701: First-in-class oral activator of systemic innate immunity combined with pembrolizumab, in patients with metastatic castration-resistant prostate cancer (mCRPC) of adenocarcinoma phenotype—Phase 2a results.
Zhang J, Aggarwal R, Tagawa S, Linch M, Petrylak D, Costin D, De Bono J, Jones R, Karsh L, Zhu X, Borderies P, Deshpande R, O'Neill V, Monk P. BXCL701: First-in-class oral activator of systemic innate immunity combined with pembrolizumab, in patients with metastatic castration-resistant prostate cancer (mCRPC) of adenocarcinoma phenotype—Phase 2a results. Journal Of Clinical Oncology 2022, 40: 125-125. DOI: 10.1200/jco.2022.40.6_suppl.125.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerAnti-tumor activityEvaluable patientsTaxane chemotherapyPrior linesAndrogen receptorProstate cancerAdenocarcinoma cohortCastration-resistant prostate cancerOral small-molecule inhibitorEncouraging anti-tumor activityBone-only diseaseComposite response rateImmune-related AEPhase 1b/2 studyPrime immune cellsSystemic innate immunityDisease control rateAcceptable safety profileMost prostate cancersAndrogen deprivation treatmentImmune effector cellsCTC conversionMeasurable diseaseRECIST 1.1A0517 Clinical outcomes of patients with metastatic Hormone-Sensitive Prostate Cancer (mHSPC) with Prostate-Specific Antigen (PSA) decline to undetectable levels on enzalutamide (ENZA): Post hoc analysis of ARCHES
Stenzl A, Shore N, Villers A, Iguchi T, Gomez-Veiga F, Alcaraz A, Alekseev B, Azad A, Szmulewitz R, Petrylak D, Holzbeierlein J, Rosbrook B, Zohren F, Haas G, Gourgioti G, El-Chaar N, Armstrong A. A0517 Clinical outcomes of patients with metastatic Hormone-Sensitive Prostate Cancer (mHSPC) with Prostate-Specific Antigen (PSA) decline to undetectable levels on enzalutamide (ENZA): Post hoc analysis of ARCHES. European Urology 2022, 81: s776-s777. DOI: 10.1016/s0302-2838(22)00600-5.Peer-Reviewed Original Research
2021
610P BXCL701 - 1st-in-class oral activator of systemic innate immunity-combined with pembrolizumab, in men with metastatic castration-resistant prostate cancer (mCRPC): Phase II results
Monk P, Zhang J, Costin D, Petrylak D, Tagawa S, Karsh L, Zhu X, Linch M, Jones R, Borderies P, O'Neill V, Aggarwal R. 610P BXCL701 - 1st-in-class oral activator of systemic innate immunity-combined with pembrolizumab, in men with metastatic castration-resistant prostate cancer (mCRPC): Phase II results. Annals Of Oncology 2021, 32: s651. DOI: 10.1016/j.annonc.2021.08.1123.Peer-Reviewed Original Research579MO CheckMate 9KD cohort A2 final analysis: Nivolumab (NIVO) + rucaparib for chemotherapy (CT)-naïve metastatic castration-resistant prostate cancer (mCRPC)
Petrylak D, Perez-Gracia J, Lacombe L, Bastos D, Mahammedi H, Kwan E, Zschäbitz S, Armstrong A, Pachynski R, Goh J, Burotto M, Gravis G, McCune S, Limón J, Retz M, Saad F, Amin N, Li J, Unsal-Kacmaz K, Fizazi K. 579MO CheckMate 9KD cohort A2 final analysis: Nivolumab (NIVO) + rucaparib for chemotherapy (CT)-naïve metastatic castration-resistant prostate cancer (mCRPC). Annals Of Oncology 2021, 32: s629-s630. DOI: 10.1016/j.annonc.2021.08.1092.Peer-Reviewed Original ResearchLBA25 Final overall survival (OS) analysis from ARCHES: A phase III, randomized, double-blind, placebo (PBO)-controlled study of enzalutamide (ENZA) + androgen deprivation therapy (ADT) in men with metastatic hormone-sensitive prostate cancer (mHSPC)
Armstrong A, Iguchi T, Azad A, Szmulewitz R, Holzbeierlein J, Villers A, Alcaraz A, Alekseev B, Shore N, Petrylak D, Rosbrook B, Zohren F, Yamada S, Haas G, Stenzl A. LBA25 Final overall survival (OS) analysis from ARCHES: A phase III, randomized, double-blind, placebo (PBO)-controlled study of enzalutamide (ENZA) + androgen deprivation therapy (ADT) in men with metastatic hormone-sensitive prostate cancer (mHSPC). Annals Of Oncology 2021, 32: s1300-s1301. DOI: 10.1016/j.annonc.2021.08.2101.Peer-Reviewed Original ResearchThe efficacy of enzalutamide (ENZA) plus androgen deprivation therapy (ADT) on bone oligometastatic hormone-sensitive prostate cancer: A post hoc analysis of ARCHES.
Armstrong A, Iguchi T, Azad A, Villers A, Alekseev B, Petrylak D, Szmulewitz R, Alcaraz A, Shore N, Holzbeierlein J, Gomez-Veiga F, Rosbrook B, Zohren F, Haas G, Gourgioti G, El-Chaar N, Stenzl A. The efficacy of enzalutamide (ENZA) plus androgen deprivation therapy (ADT) on bone oligometastatic hormone-sensitive prostate cancer: A post hoc analysis of ARCHES. Journal Of Clinical Oncology 2021, 39: 5071-5071. DOI: 10.1200/jco.2021.39.15_suppl.5071.Peer-Reviewed Original ResearchMetastatic hormone-sensitive prostate cancerAndrogen deprivation therapyEfficacy of enzalutamideHormone-sensitive prostate cancerBone metastasesTreatment armsProstate cancerOligometastatic hormone-sensitive prostate cancerPrior docetaxel chemotherapySecondary clinical outcomesDeprivation therapyEfficacy outcomesRadiographic progressionSecondary endpointsBaseline characteristicsDisease volumeDocetaxel chemotherapyMetastatic burdenPolymetastatic diseaseArch studyClinical outcomesCentral reviewClinical benefitSafety profilePlaceboCheckMate 9KD Arm B final analysis: Efficacy and safety of nivolumab plus docetaxel for chemotherapy-naïve metastatic castration-resistant prostate cancer.
Fizazi K, González Mella P, Castellano D, Minatta J, Rezazadeh A, Shaffer D, Vazquez Limon J, Sánchez López H, Armstrong A, Horvath L, Dzik C, Amin N, Li J, Unsal-Kacmaz K, Retz M, Saad F, Petrylak D, Pachynski R. CheckMate 9KD Arm B final analysis: Efficacy and safety of nivolumab plus docetaxel for chemotherapy-naïve metastatic castration-resistant prostate cancer. Journal Of Clinical Oncology 2021, 39: 12-12. DOI: 10.1200/jco.2021.39.6_suppl.12.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerTreatment-related AEsObjective response rateChemotherapy-naïve metastatic castration-resistant prostate cancerRadiographic progression-free survivalCastration-resistant prostate cancerMeasurable diseaseOverall survivalArm BProstate cancerMedian numberChemotherapy-naive metastatic castration-resistant prostate cancerDisease progression/unacceptable toxicityProstate-specific antigen (PSA) response rateResponse rateComparable objective response rateOngoing androgen deprivation therapyProgression/unacceptable toxicityImmune-related AESafety of nivolumabTreatment-related deathsAndrogen deprivation therapyPhase 2 trialProgression-free survivalAntitumor immune responsePhase I study of AMG 509, a STEAP1 x CD3 T-cell recruiting XmAb 2+1 immune therapy, in patients with metastatic castration-resistant prostate cancer (mCRPC).
Kelly W, Pook D, Appleman L, Waterhouse D, Horvath L, Edenfield W, Matsubara N, Danila D, Aggarwal R, Petrylak D, Sartor A, Sumey C, Adra N, Armstrong A, Cheng F, Stieglmaier J, Kouros-Mehr H, Dorff T. Phase I study of AMG 509, a STEAP1 x CD3 T-cell recruiting XmAb 2+1 immune therapy, in patients with metastatic castration-resistant prostate cancer (mCRPC). Journal Of Clinical Oncology 2021, 39: tps183-tps183. DOI: 10.1200/jco.2021.39.6_suppl.tps183.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerFirst doseImmune therapyProstate cancerECOG performance status 0Prostate-specific antigen (PSA) responseCastration-resistant prostate cancerT cell-mediated lysisDose-expansion phasePerformance status 0Phase 2 doseObjective tumor responseT effector cellsASCO Annual MeetingTotal serum testosteroneLogistic regression modelsCell surface antigensTransmembrane epithelial antigenTumor cell responseCNS metastasisLeptomeningeal diseaseRECIST 1.1Status 0Taxane regimensHormonal therapy