2022
Synergistic activity of neratinib in combination with olaparib in uterine serous carcinoma overexpressing HER2/neu
Yadav G, Roque DM, Bellone S, Manavella DD, Hartwich TMP, Zipponi M, Harold J, Tymon-Rosario J, Mutlu L, Altwerger G, Menderes G, Ratner E, Buza N, Hui P, Huang GS, Andikyan V, Clark M, Azodi M, Schwartz PE, Alexandrov LB, Santin AD. Synergistic activity of neratinib in combination with olaparib in uterine serous carcinoma overexpressing HER2/neu. Gynecologic Oncology 2022, 166: 351-357. PMID: 35641325, DOI: 10.1016/j.ygyno.2022.05.021.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaHER2/neu expressionHER2/neuCombination of olaparibUSC xenograftsUSC cell linesNeu expressionSerous carcinomaLow HER2/neu expressionHER2/neu 3Cell linesHER2/neu gene amplificationNovel therapeutic optionsPolymerase inhibitor olaparibNeu gene amplificationDurable growth inhibitionNeratinib treatmentUSC cellsUSC patientsEndometrial cancerAggressive variantTherapeutic optionsPoor prognosisHER2/Single agent
2021
DHES0815A, a novel antibody-drug conjugate targeting HER2/neu, is highly active against uterine serous carcinomas in vitro and in vivo
Tymon-Rosario J, Bonazzoli E, Bellone S, Manzano A, Pelligra S, Guglielmi A, Gnutti B, Nagarkatti N, Zeybek B, Manara P, Zammataro L, Harold J, Mauricio D, Buza N, Hui P, Altwerger G, Menderes G, Ratner E, Clark M, Andikyan V, Huang GS, Silasi DA, Azodi M, Schwartz PE, Santin AD. DHES0815A, a novel antibody-drug conjugate targeting HER2/neu, is highly active against uterine serous carcinomas in vitro and in vivo. Gynecologic Oncology 2021, 163: 334-341. PMID: 34452746, PMCID: PMC8722447, DOI: 10.1016/j.ygyno.2021.08.014.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedBenzodiazepinesBystander EffectCell Line, TumorCystadenocarcinoma, SerousDrug Resistance, NeoplasmFemaleHumansImmunoconjugatesMiddle AgedPrimary Cell CultureReceptor, ErbB-2TrastuzumabUterine NeoplasmsXenograft Model Antitumor AssaysConceptsHER2/neuPrimary USC cell linesUSC cell linesUterine serous carcinomaSerous carcinomaHER2/Cell linesBystander killingHER2/neu protein expressionHER2/neu overexpressionProtein expressionNovel treatment optionsAggressive histologic variantNeu protein expressionHER2 protein expressionC-erbB2 gene amplificationSignificant bystander killingUSC xenograftsEndometrial cancerNegative tumorsPoor prognosisPositive tumorsTreatment optionsPreclinical activityHistologic variantsTrastuzumab tolerability in the treatment of advanced (stage III-IV) or recurrent uterine serous carcinomas that overexpress HER2/neu
Tymon-Rosario J, Siegel ER, Bellone S, Harold J, Adjei N, Zeybek B, Mauricio D, Altwerger G, Menderes G, Ratner E, Clark M, Andikyan V, Huang GS, Azodi M, Schwartz PE, Fader AN, Santin AD. Trastuzumab tolerability in the treatment of advanced (stage III-IV) or recurrent uterine serous carcinomas that overexpress HER2/neu. Gynecologic Oncology 2021, 163: 93-99. PMID: 34372971, PMCID: PMC8721852, DOI: 10.1016/j.ygyno.2021.07.033.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaRecurrent uterine serous carcinomaAdverse eventsTreatment armsSerous carcinomaExperimental armToxicity profileTreatment-related adverse eventsTrastuzumab maintenance therapyCarboplatin/paclitaxelCardiac adverse eventsEndometrial cancer patientsGastrointestinal adverse eventsManageable toxicity profilePhase II trialEfficacy of trastuzumabSystem organ classII trialMaintenance therapyPrimary endpointSecondary endpointsMaintenance treatmentSafety profileCancer patientsCumulative toxicity
2020
Randomized Phase II Trial of Carboplatin–Paclitaxel Compared with Carboplatin–Paclitaxel–Trastuzumab in Advanced (Stage III–IV) or Recurrent Uterine Serous Carcinomas that Overexpress Her2/Neu (NCT01367002): Updated Overall Survival Analysis
Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, Chambers S, Secord AA, Havrilesky L, O'Malley DM, Backes FJ, Nevadunsky N, Edraki B, Pikaart D, Lowery W, ElSahwi K, Celano P, Bellone S, Azodi M, Litkouhi B, Ratner E, Silasi DA, Schwartz PE, Santin AD. Randomized Phase II Trial of Carboplatin–Paclitaxel Compared with Carboplatin–Paclitaxel–Trastuzumab in Advanced (Stage III–IV) or Recurrent Uterine Serous Carcinomas that Overexpress Her2/Neu (NCT01367002): Updated Overall Survival Analysis. Clinical Cancer Research 2020, 26: 3928-3935. PMID: 32601075, PMCID: PMC8792803, DOI: 10.1158/1078-0432.ccr-20-0953.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsCarboplatinChemotherapy, AdjuvantCystadenocarcinoma, SerousCytoreduction Surgical ProceduresDrug Administration ScheduleEndometrial NeoplasmsEndometriumFemaleFollow-Up StudiesHumansMiddle AgedNeoplasm Recurrence, LocalNeoplasm StagingPaclitaxelProgression-Free SurvivalReceptor, ErbB-2Survival AnalysisTrastuzumabConceptsProgression-free survivalRandomized phase II trialPhase II trialOverall survivalHER2/neuStage IIICarboplatin-paclitaxelII trialRecurrent diseaseControl armSurvival analysisRecurrent uterine serous carcinomaCarboplatin/paclitaxelUterine serous carcinomaOverall survival analysisEvaluable patientsEligible patientsPrimary endpointSecondary endpointsEndometrial cancerAggressive variantSerous carcinomaPrimary treatmentSurvival medianPatientsStage III uterine serous carcinoma: modern trends in multimodality treatment
Li JY, Young MR, Huang G, Litkouhi B, Santin A, Schwartz PE, Damast S. Stage III uterine serous carcinoma: modern trends in multimodality treatment. Journal Of Gynecologic Oncology 2020, 31: e53. PMID: 32266802, PMCID: PMC7286763, DOI: 10.3802/jgo.2020.31.e53.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaExternal beam RTVaginal brachytherapyOverall survivalHuman epidermal growth factor receptorModern treatment eraSentinel node samplingRegional nodal recurrenceKaplan-Meier estimatesLog-rank testCox proportional hazardsExternal beam radiotherapyEpidermal growth factor receptorERA treatmentGrowth factor receptorUSC patientsFree survivalNodal recurrenceTreatment eraMultimodality treatmentPatient characteristicsPerioperative periodRegional nodalSerous carcinomaNode samplingSelection of HER2/NEU negative tumor cells as a mechanism of resistance to trastuzumab in uterine serous carcinoma
Pelligra S, Buza N, Hui P, Bellone S, Zeybek B, Ratner E, Schwartz PE, Scambia G, Santin AD. Selection of HER2/NEU negative tumor cells as a mechanism of resistance to trastuzumab in uterine serous carcinoma. Gynecologic Oncology Reports 2020, 32: 100554. PMID: 32140533, PMCID: PMC7049633, DOI: 10.1016/j.gore.2020.100554.Peer-Reviewed Original ResearchUterine serous carcinomaHER2/neuNegative tumor cellsUSC patientsTumor cellsSerous carcinomaHER2/neu overexpressionCarboplatin/paclitaxelInitial clinical responsePost-treatment biopsiesHumanized monoclonal antibodyC-erbB2 gene amplificationNCCN guidelinesClinical responseEndometrial cancerPreferred regimenAggressive variantMechanisms of resistanceNeu overexpressionRecurrent/HER2/TrastuzumabPatientsMonoclonal antibodiesNeu
2019
In vitro and in vivo activity of sacituzumab govitecan, an antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (Trop-2) in uterine serous carcinoma
Han C, Perrone E, Zeybek B, Bellone S, Tymon-Rosario J, Altwerger G, Menderes G, Feinberg J, Haines K, Muller Karger ME, Bianchi A, Zammataro L, Manzano A, Bonazzoli E, Manara P, Buza N, Hui P, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Lopez S, Santin AD. In vitro and in vivo activity of sacituzumab govitecan, an antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (Trop-2) in uterine serous carcinoma. Gynecologic Oncology 2019, 156: 430-438. PMID: 31839338, DOI: 10.1016/j.ygyno.2019.11.018.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntigens, NeoplasmCamptothecinCell Adhesion MoleculesCell Line, TumorCystadenocarcinoma, SerousFemaleFlow CytometryHumansImmunoconjugatesImmunohistochemistryMiceMice, SCIDMolecular Targeted TherapyRandom AllocationTissue Array AnalysisUterine NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous carcinomaCell surface antigen 2Sacituzumab govitecanTrop-2 expressionTrop-2Serous carcinomaAntigen 2Advanced/recurrent diseasePrimary uterine serous carcinomaResistant human tumorsSignificant bystander killingUSC patientsUSC xenograftsRecurrent diseaseClinical responseEndometrial cancerAggressive variantPoor prognosisPreclinical activityPrimary tumorIntravenous administrationClinical developmentUSC samplesActive metaboliteSN-38