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 interventionPatientsAvelumab 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 endpointAvelumab 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 cutoff
2023
Efficacy of sacituzumab govitecan (SG) in locally advanced (LA) or metastatic urothelial cancer (mUC) by trophoblast cell surface antigen 2 (Trop-2) expression.
Loriot Y, Balar A, Petrylak D, Rezazadeh A, Grivas P, Flechon A, Jain R, Agarwal N, Bupathi M, Barthelemy P, Beuzeboc P, Palmbos P, Kyriakopoulos C, Pouessel D, Sternberg C, Tonelli J, Elboudwarej E, Diehl L, Jürgensmeier J, Tagawa S. Efficacy of sacituzumab govitecan (SG) in locally advanced (LA) or metastatic urothelial cancer (mUC) by trophoblast cell surface antigen 2 (Trop-2) expression. Journal Of Clinical Oncology 2023, 41: 4579-4579. DOI: 10.1200/jco.2023.41.16_suppl.4579.Peer-Reviewed Original ResearchObjective response rateMetastatic urothelial cancerProgression-free survivalTrop-2 expressionMedian progression-free survivalSacituzumab govitecanArchival tumor samplesH-scoreCheckpoint inhibitorsUnstratified Cox proportional hazards modelAnti-Trop-2 antibodyTrop-2 protein expressionTumor samplesCox proportional hazards modelTumor cellsAccelerated FDA approvalOverall survival rateC1-3Proportional hazards modelMedian OSBaseline characteristicsData cutoffEfficacy endpointEfficacy outcomesPrimary endpointFirst-in-class oral innate immune activator BXCL701 combined with pembrolizumab, in patients with metastatic castration-resistant prostate cancer (mCRPC) of small cell neuroendocrine (SCNC) variant: Randomized phase 2b trial.
Aggarwal R, Zhang J, Monk P, Zhu X, Costin D, Petrylak D, Borderies P, Deshpande R, Hafeez A, O'Neill V, Tagawa S. First-in-class oral innate immune activator BXCL701 combined with pembrolizumab, in patients with metastatic castration-resistant prostate cancer (mCRPC) of small cell neuroendocrine (SCNC) variant: Randomized phase 2b trial. Journal Of Clinical Oncology 2023, 41: tps5109-tps5109. DOI: 10.1200/jco.2023.41.16_suppl.tps5109.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerSerious adverse eventsPartial responsePrimary endpointPhase 2aRandomized Phase 2b TrialCastration-resistant prostate cancerOral small-molecule inhibitorPhase 2b trialPrime immune cellsRECIST 1.1 criteriaDisease control rateImmune checkpoint inhibitorsPhase 2 studyPlatinum-based chemotherapyDuration of responsePotential predictive biomarkersImmune effector cellsMeasurable diseaseNeuroendocrine variantPSA-PFSRECIST 1.1Safety populationCheckpoint inhibitorsData cutoffPatient-reported outcomes (PROs) in KEYNOTE-921: Pembrolizumab (pembro) plus docetaxel for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).
Petrylak D, Ratta R, Matsubara N, Korbenfeld E, Gafanov R, Mourey L, Todenhöfer T, Gurney H, Kramer G, Bergman A, Zalewski P, De Santis M, Armstrong A, Gerritsen W, Pachynski R, Saretsky T, Ghate S, Li X, Schloss C, Fizazi K. Patient-reported outcomes (PROs) in KEYNOTE-921: Pembrolizumab (pembro) plus docetaxel for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). Journal Of Clinical Oncology 2023, 41: 129-129. DOI: 10.1200/jco.2023.41.6_suppl.129.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerPatient-reported outcomesBPI-SF scoresBPI-SFTotal scoreWk 24Wk 27Castration-resistant prostate cancerPrespecified secondary end pointsEnd pointExploratory end pointsFACT-G totalPrespecified final analysisSecondary end pointsOverall improvement rateSubscale scoresMedian TTPPPain progressionData cutoffAgent therapyMedian timeAnalysis populationStudy treatmentSymptom scoresTrial armsUpdated outcomes in TROPHY-U-01 cohort 1, a phase 2 study of sacituzumab govitecan (SG) in patients (pts) with metastatic urothelial cancer (mUC) that progressed after platinum (PT)-based chemotherapy and a checkpoint inhibitor (CPI).
Tagawa S, Balar A, Petrylak D, Rezazadeh A, Loriot Y, Flechon A, Jain R, Agarwal N, Bupathi M, Barthelemy P, Beuzeboc P, Palmbos P, Kyriakopoulos C, Pouessel D, Sternberg C, Tonelli J, Sierecki M, Zhou H, Grivas P. Updated outcomes in TROPHY-U-01 cohort 1, a phase 2 study of sacituzumab govitecan (SG) in patients (pts) with metastatic urothelial cancer (mUC) that progressed after platinum (PT)-based chemotherapy and a checkpoint inhibitor (CPI). Journal Of Clinical Oncology 2023, 41: 526-526. DOI: 10.1200/jco.2023.41.6_suppl.526.Peer-Reviewed Original ResearchMetastatic urothelial cancerTreatment-related adverse eventsObjective response rateProgression-free survivalDuration of responseClinical benefit ratePhase 2 studyCheckpoint inhibitorsSacituzumab govitecanOverall survivalPrior therapyCentral reviewResponse rateAnti-Trop-2 antibodyAccelerated FDA approvalECOG PS 0Last prior therapyTreatment-related deathsKey secondary endpointNew safety signalsFebrile neutropeniaOS ratesData cutoffPrimary endpointRECIST 1.1
2022
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.
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
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
First-in-human phase I study of ARV-110, an androgen receptor (AR) PROTAC degrader in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC) following enzalutamide (ENZ) and/or abiraterone (ABI).
Petrylak D, Gao X, Vogelzang N, Garfield M, Taylor I, Dougan Moore M, Peck R, Burris H. First-in-human phase I study of ARV-110, an androgen receptor (AR) PROTAC degrader in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC) following enzalutamide (ENZ) and/or abiraterone (ABI). Journal Of Clinical Oncology 2020, 38: 3500-3500. DOI: 10.1200/jco.2020.38.15_suppl.3500.Peer-Reviewed Original ResearchMetastatic castrate-resistant prostate cancerAST/ALTAdverse eventsPSA responseAnti-tumor activityPrior therapyAST/ALT elevationElevated AST/ALTCastrate-resistant prostate cancerProstate cancer xenograft modelPreclinical anti-tumor activityPhase 2 doseRECIST partial responseAcceptable safety profileAcute renal failureHuman phase ICancer xenograft modelPrior chemotherapyALT elevationData cutoffRenal failurePartial responseDose escalationRadium-223Enz resistanceAnalysis 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
Durability of complete response (CR) with atezolizumab (atezo) in locally advanced/metastatic urothelial carcinoma (mUC).
Loriot Y, Balar A, Dreicer R, Hoffman-Censits J, Perez-Gracia J, Petrylak D, Van Der Heijden M, Shen X, Zhu Q, Ding B, Kaiser C, Rosenberg J. Durability of complete response (CR) with atezolizumab (atezo) in locally advanced/metastatic urothelial carcinoma (mUC). Journal Of Clinical Oncology 2019, 37: 4527-4527. DOI: 10.1200/jco.2019.37.15_suppl.4527.Peer-Reviewed Original Research
2018
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.
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
2016
IMvigor 210, a phase II trial of atezolizumab (MPDL3280A) in platinum-treated locally advanced or metastatic urothelial carcinoma (mUC).
Hoffman-Censits J, Grivas P, Van Der Heijden M, Dreicer R, Loriot Y, Retz M, Vogelzang N, Perez-Gracia J, Rezazadeh A, Bracarda S, Yu E, Hoimes C, Bellmunt J, Quinn D, Petrylak D, Hussain S, Cui N, Mariathasan S, Abidoye O, Rosenberg J. IMvigor 210, a phase II trial of atezolizumab (MPDL3280A) in platinum-treated locally advanced or metastatic urothelial carcinoma (mUC). Journal Of Clinical Oncology 2016, 34: 355-355. DOI: 10.1200/jco.2016.34.2_suppl.355.Peer-Reviewed Original ResearchMetastatic urothelial carcinomaPoor prognostic factorPrognostic factorsPD-L1Prognostic subgroupsPD-L1/PDImmune cell statusMedian treatment durationPD-L1 subgroupsTreatment-related AEsPD-L1 expressionPD-L1 statusPhase II trialPlatinum-based chemotherapyCo-primary endpointsPoor prognostic subgroupMUC patientsRECIST v1.1Data cutoffDurable responsesII trialAntitumor immunityG3-4Median ageHistoric controls
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
2013
A phase I/II study of safety and efficacy of orteronel (TAK-700), an oral, investigational, nonsteroidal 17,20-lyase inhibitor, with docetaxel and prednisone (DP) in metastatic castration-resistant prostate cancer (mCRPC): Updated phase II results.
Petrylak D, Gandhi J, Clark W, Heath E, Lin J, Oh W, Agus D, Carthon B, Moran S, Kong N, Suri A, Bargfrede M, Liu G. A phase I/II study of safety and efficacy of orteronel (TAK-700), an oral, investigational, nonsteroidal 17,20-lyase inhibitor, with docetaxel and prednisone (DP) in metastatic castration-resistant prostate cancer (mCRPC): Updated phase II results. Journal Of Clinical Oncology 2013, 31: 59-59. DOI: 10.1200/jco.2013.31.6_suppl.59.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerPSA responseMedian timePhase I/II studyCastration-resistant prostate cancerDrug-related SAEsECOG PS 0/1Good PSA responseProgression of PsAPhase 1/2 studyPartial tumor responsePhase II resultsBlood alkaline phosphataseCastrate menPS 0/1Median PSAPrior chemotherapyPSA declinePSA progressionRadiologic progressionRECIST 1.1Data cutoffII studyRadiographic diseaseSerum PSA
2012
918P Phase 2 Results from a Phase 1/2 Study of Tak-700 (ORTERONEL), An Oral, Investigational, Nonsteroidal 17,20-Lyase Inhibitor, with Docetaxel and Prednisone (DP) in Metastatic Castration-Resistant Prostate Cancer (MCRPC)
Petrylak D, Gandhi J, Clark W, Heath E, Lin J, Oh W, Agus D, Carthon B, Moran S, Liu G. 918P Phase 2 Results from a Phase 1/2 Study of Tak-700 (ORTERONEL), An Oral, Investigational, Nonsteroidal 17,20-Lyase Inhibitor, with Docetaxel and Prednisone (DP) in Metastatic Castration-Resistant Prostate Cancer (MCRPC). Annals Of Oncology 2012, 23: ix302-ix303. DOI: 10.1016/s0923-7534(20)33476-1.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerPhase 1/2 studyTAK-700Febrile neutropeniaMedian timeCastration-resistant prostate cancerDrug-related SAEsECOG PS 0/1Good PSA responseProgression of PsAPSA response rateTreatment-related AEsPartial tumor responseLyase inhibitorMillennium PharmaceuticalsGlaxo Smith KlineCastrate menEvaluable populationPrior chemotherapyPS 0/1PSA declinePSA progressionRadiologic progressionRECIST 1.1Data cutoff