2020
Selection 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
2018
LBA36 Association of PD-L1 expression and gene expression profiling with clinical response to pembrolizumab in patients with advanced recurrent ovarian cancer: Results from the phase II KEYNOTE-100 study
Ledermann J, Shapira-Frommer R, Santin A, Lisyanskaya A, Pignata S, Vergote I, Raspagliesi F, Sonke G, Birrer M, Provencher D, Sehouli J, Colombo N, González-Martín A, Oaknin A, Ottevanger P, Rudaitis V, Cristescu R, Kobie J, Ruman J, Matulonis U. LBA36 Association of PD-L1 expression and gene expression profiling with clinical response to pembrolizumab in patients with advanced recurrent ovarian cancer: Results from the phase II KEYNOTE-100 study. Annals Of Oncology 2018, 29: viii728. DOI: 10.1093/annonc/mdy424.043.Peer-Reviewed Original ResearchExceptional Response to Pembrolizumab in a Metastatic, Chemotherapy/Radiation-Resistant Ovarian Cancer Patient Harboring a PD-L1-Genetic Rearrangement
Bellone S, Buza N, Choi J, Zammataro L, Gay L, Elvin J, Rimm DL, Liu Y, Ratner E, Schwartz PE, Santin AD. Exceptional Response to Pembrolizumab in a Metastatic, Chemotherapy/Radiation-Resistant Ovarian Cancer Patient Harboring a PD-L1-Genetic Rearrangement. Clinical Cancer Research 2018, 24: 3282-3291. PMID: 29351920, PMCID: PMC6050068, DOI: 10.1158/1078-0432.ccr-17-1805.Peer-Reviewed Original ResearchMeSH KeywordsAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorBiopsyComputational BiologyDrug Resistance, NeoplasmExome SequencingFemaleGene RearrangementHLA AntigensHumansMolecular Targeted TherapyMutationOvarian NeoplasmsPositron Emission Tomography Computed TomographyProgrammed Cell Death 1 ReceptorReceptors, Cell SurfaceRetreatmentT-LymphocytesTreatment OutcomeConceptsImmune checkpoint inhibitor pembrolizumabCheckpoint inhibitor pembrolizumabComplete clinical responseClinical responsePD-L1Ovarian carcinomaAberrant PD-L1 expressionPD-L1 surface expressionAnti-PD1 inhibitorsPD-L1 expressionRemarkable clinical responsesHigh-grade ovarian carcinomaStandard treatment modalityAlternative therapeutic optionClear cell featuresNovel treatment optionsSignificant side effectsT-cell lymphocytesWhole exome sequencing techniqueClin Cancer ResMetastatic human tumorsRecurrent diseaseComplete responseHeavy infiltrationTherapeutic optionsBinimetinib (MEK162) in recurrent low-grade serous ovarian cancer resistant to chemotherapy and hormonal treatment
Han C, Bellone S, Zammataro L, Schwartz PE, Santin AD. Binimetinib (MEK162) in recurrent low-grade serous ovarian cancer resistant to chemotherapy and hormonal treatment. Gynecologic Oncology Reports 2018, 25: 41-44. PMID: 29946554, PMCID: PMC6014583, DOI: 10.1016/j.gore.2018.05.011.Peer-Reviewed Original ResearchLow-grade serous ovarian carcinomaTreatment optionsHormonal treatmentRecurrent low-grade serous ovarian cancerRecurrent low-grade serous ovarian carcinomaLow-grade serous ovarian cancerDramatic clinical responseDrug-related toxicityEffective treatment optionNew treatment optionsSerial CT scansSerous ovarian cancerSerous ovarian carcinomaMitogen-activated protein kinase inhibitorOral steroidsRECIST 1.1Clinical responseMultiple chemotherapyOvarian carcinomaTarget lesionsOvarian cancerCT scanResponse durationBinimetinibKRAS G12Sacituzumab Govitecan (IMMU-132) in treatment-resistant uterine serous carcinoma: A case report
Han C, Bellone S, Schwartz PE, Govindan SV, Sharkey RM, Goldenberg DM, Santin AD. Sacituzumab Govitecan (IMMU-132) in treatment-resistant uterine serous carcinoma: A case report. Gynecologic Oncology Reports 2018, 25: 37-40. PMID: 29977989, PMCID: PMC6030029, DOI: 10.1016/j.gore.2018.05.009.Peer-Reviewed Original ResearchUterine serous carcinomaSacituzumab govitecanAntibody-drug conjugatesSerous carcinomaTreatment optionsNovel antibody-drug conjugateTreatment-resistant diseaseImpressive clinical responsesSignificant adverse eventsEffective treatment optionNew treatment optionsSerial CT scansUSC patientsAdverse eventsClinical responseMultiple chemotherapyAggressive variantCase reportUterine cancerClinical trialsCT scanDramatic responseSurface antigenTrop-2Chemotherapy
2016
Regression of metastatic, radiation/chemotherapy-resistant uterine serous carcinoma overexpressing HER2/neu with trastuzumab emtansine (TDM-1)
Santin AD, Bellone S, Buza N, Schwartz PE. Regression of metastatic, radiation/chemotherapy-resistant uterine serous carcinoma overexpressing HER2/neu with trastuzumab emtansine (TDM-1). Gynecologic Oncology Reports 2016, 19: 10-12. PMID: 28018954, PMCID: PMC5175991, DOI: 10.1016/j.gore.2016.12.003.Peer-Reviewed Original ResearchTDM-1Remarkable clinical responsesAlternative therapeutic optionUterine serous carcinomaNovel treatment optionsAbdominal wall musclesUSC patientsClinical responseTumor depositsSerous carcinomaTherapeutic optionsTreatment optionsTrastuzumab emtansineComplete resolutionCAT scanSystemic controlWall musclesPatientsCarcinomaHER2NeuChemotherapyEmtansineSurgeryOptionsRegression of Chemotherapy-Resistant Polymerase ϵ (POLE) Ultra-Mutated and MSH6 Hyper-Mutated Endometrial Tumors with Nivolumab
Santin AD, Bellone S, Buza N, Choi J, Schwartz PE, Schlessinger J, Lifton RP. Regression of Chemotherapy-Resistant Polymerase ϵ (POLE) Ultra-Mutated and MSH6 Hyper-Mutated Endometrial Tumors with Nivolumab. Clinical Cancer Research 2016, 22: 5682-5687. PMID: 27486176, PMCID: PMC5135588, DOI: 10.1158/1078-0432.ccr-16-1031.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitor nivolumabCheckpoint inhibitor nivolumabClinical responseInhibitor nivolumabAnti-PD-1 inhibitorsHyper-mutated tumorsPatient's clinical responseRemarkable clinical responsesAlternative therapeutic optionNovel treatment optionsRecurrent/metastaticHigh side effectsRecurrent diseaseEndometrial carcinomaTherapeutic optionsTreatment optionsModern chemotherapyGrade 3Side effectsPatientsHuman tumorsTumorsGene mutationsNivolumabChemotherapy
2014
HER2/neu in Endometrial Cancer: A Promising Therapeutic Target With Diagnostic Challenges
Buza N, Roque DM, Santin AD. HER2/neu in Endometrial Cancer: A Promising Therapeutic Target With Diagnostic Challenges. Archives Of Pathology & Laboratory Medicine 2014, 138: 343-50. PMID: 24576030, DOI: 10.5858/arpa.2012-0416-ra.Peer-Reviewed Original ResearchConceptsEndometrial carcinomaHER2/neuPromising therapeutic targetHER2 testingClinical responseTherapeutic targetHumanized monoclonal immunoglobulin G1 antibodyMonoclonal immunoglobulin G1 antibodyUterine serous carcinomaImmunoglobulin G1 antibodyNovel therapeutic strategiesEndometrial cancerSerous adenocarcinomaSerous carcinomaCase reportDiagnostic challengeHER2 overexpressionPathogenetic featuresClinical studiesG1 antibodyTherapeutic strategiesCarcinomaTherapeutic efficacyStandardized criteriaTherapy
2011
Phase II trial of cetuximab in the treatment of persistent or recurrent squamous or non-squamous cell carcinoma of the cervix: A Gynecologic Oncology Group study
Santin AD, Sill MW, McMeekin DS, Leitao MM, Brown J, Sutton GP, Van Le L, Griffin P, Boardman CH. Phase II trial of cetuximab in the treatment of persistent or recurrent squamous or non-squamous cell carcinoma of the cervix: A Gynecologic Oncology Group study. Gynecologic Oncology 2011, 122: 495-500. PMID: 21684583, PMCID: PMC3152667, DOI: 10.1016/j.ygyno.2011.05.040.Peer-Reviewed Original ResearchConceptsProgression-free survivalGynecologic Oncology GroupPhase II trialSquamous cell histologyII trialCell histologyCell carcinomaGrade 3 adverse eventsMedian progression-free survivalGynecologic Oncology Group studyNon-squamous cell carcinomaGOG performance statusOverall survival timeSquamous cell carcinomaEGFR antibody cetuximabEligible patientsMeasurable diseasePrimary endpointPrior radiationProhibitive toxicityAdverse eventsClinical responseOncology GroupPerformance statusRecurrent carcinoma
2008
Trastuzumab treatment in patients with advanced or recurrent endometrial carcinoma overexpressing HER2/neu
Santin AD, Bellone S, Roman JJ, McKenney JK, Pecorelli S. Trastuzumab treatment in patients with advanced or recurrent endometrial carcinoma overexpressing HER2/neu. International Journal Of Gynecology & Obstetrics 2008, 102: 128-131. PMID: 18555254, DOI: 10.1016/j.ijgo.2008.04.008.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsCA-125 AntigenDisease ProgressionEndometrial NeoplasmsFemaleGene Expression Regulation, NeoplasticGenes, erbB-2HumansImmunohistochemistryIn Situ Hybridization, FluorescenceNeoplasm Recurrence, LocalReceptor, ErbB-2TrastuzumabConceptsMetastatic endometrial carcinomaHER2/neuEndometrial carcinomaSingle agentCA-125 evaluationHER2/neu receptorRecurrent metastatic diseaseRecurrent endometrial carcinomaEffect of trastuzumabSerial CT scansViable therapeutic optionC-erbB2 gene amplificationSalvage chemotherapyClinical responseMetastatic diseaseTrastuzumab treatmentTherapeutic optionsStudy criteriaDisease progressionCT scanPatientsTrastuzumabNeu receptorChemotherapyRadiation treatment
2005
HPV16/18 E7-pulsed dendritic cell vaccination in cervical cancer patients with recurrent disease refractory to standard treatment modalities
Santin AD, Bellone S, Palmieri M, Ravaggi A, Romani C, Tassi R, Roman JJ, Burnett A, Pecorelli S, Cannon MJ. HPV16/18 E7-pulsed dendritic cell vaccination in cervical cancer patients with recurrent disease refractory to standard treatment modalities. Gynecologic Oncology 2005, 100: 469-478. PMID: 16249018, DOI: 10.1016/j.ygyno.2005.09.040.Peer-Reviewed Original ResearchConceptsCervical cancer patientsStandard treatment modalityAutologous dendritic cellsT cell responsesDendritic cellsCancer patientsTreatment modalitiesHPV16/18 E7Clinical responseIFN-gammaAutologous monocyte-derived dendritic cellsE7 oncoproteinsLate-stage cervical cancer patientsCell responsesMonocyte-derived dendritic cellsHuman recombinant interleukin-2Active vaccination strategiesHPV18 E7 oncoproteinLimited tumor burdenTreatment-induced immunosuppressionAutologous tumor cellsDendritic cell vaccinationObjective clinical responsesEarly-stage diseaseType hypersensitivity reaction