2024
Unmet needs in cervical cancer – can biological therapies plug the gap?
Greenman M, Chang Y, McNamara B, Mutlu L, Santin A. Unmet needs in cervical cancer – can biological therapies plug the gap? Expert Opinion On Biological Therapy 2024, 24: 995-1003. PMID: 39311611, DOI: 10.1080/14712598.2024.2408754.Peer-Reviewed Original ResearchBiologic therapyCervical cancerIntroduction of biologic therapiesManagement of cervical cancerImmune checkpoint inhibitorsIncreased overall survivalCurrent treatment recommendationsMultiple tumor typesAntibody-drug conjugatesCheckpoint inhibitorsOverall survivalRecurrent diseaseGynecologic malignanciesTreat malignanciesTumor typesClinical outcomesAngiogenesis inhibitorsBurden of casesTreatment recommendationsTherapyImprove current standardsAntitumor activityInadequate screeningCancerMalignancySacituzumab govitecan in heavily pretreated, platinum-resistant high grade serous ovarian cancer
Greenman M, Bellone S, Demirkiran C, Hartwich T, Santin A. Sacituzumab govitecan in heavily pretreated, platinum-resistant high grade serous ovarian cancer. Gynecologic Oncology Reports 2024, 54: 101459. PMID: 39108617, PMCID: PMC11300917, DOI: 10.1016/j.gore.2024.101459.Peer-Reviewed Original ResearchHigh grade serous ovarian cancerAntibody-drug conjugatesSerous ovarian cancerSacituzumab govitecanOvarian cancerTreatment optionsPlatinum-resistant ovarian cancer patientsDose-limiting toxicityOvarian cancer patientsNovel treatment optionsPartial responseRecurrent diseaseDose reductionCancer patientsClinical trialsBackground treatmentTargeted treatmentChemotherapyTreatmentCancerDoseDiseaseOptionsTrop2PatientsTrastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate, demonstrates in vitro and in vivo antitumor activity against primary and metastatic ovarian tumors overexpressing HER2
Mutlu L, McNamara B, Bellone S, Manavella D, Demirkiran C, Greenman M, Verzosa M, Buza N, Hui P, Hartwich T, Harold J, Yang-Hartwich Y, Zipponi M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Schwartz P, Santin A. Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate, demonstrates in vitro and in vivo antitumor activity against primary and metastatic ovarian tumors overexpressing HER2. Clinical & Experimental Metastasis 2024, 41: 765-775. PMID: 38909139, DOI: 10.1007/s10585-024-10297-z.Peer-Reviewed Original ResearchHigh-grade serous ovarian cancerClear cell carcinomaHER2-targeting antibody-drug conjugateAntibody-drug conjugatesT-DXdReceptor over-expressionTrastuzumab deruxtecanXenograft modelCell linesOvarian clear cell carcinomaOvarian cancer cell linesTumors overexpressing HER2Biologically aggressive tumorsFluorescence in situ hybridization assaySerous ovarian cancerEffective antibody-drug conjugatesIn vivo antitumor activityMouse xenograft modelMetastatic cell linesDS-8201aCancer cell linesAggressive tumorsHER2 expressionCell carcinomaOvarian cancer
2023
Antibody–Drug Conjugates (ADC) in HER2/neu-Positive Gynecologic Tumors
McNamara B, Greenman M, Pebley N, Mutlu L, Santin A. Antibody–Drug Conjugates (ADC) in HER2/neu-Positive Gynecologic Tumors. Molecules 2023, 28: 7389. PMID: 37959808, PMCID: PMC10650896, DOI: 10.3390/molecules28217389.Peer-Reviewed Original ResearchConceptsHuman epidermal growth factor 2Antibody-drug conjugatesGynecologic tumorsEpidermal growth factor 2Receptor-targeting antibodiesOngoing clinical trialsRelevant preclinical studiesAnti-cancer therapyADC resistanceGynecologic malignanciesGrowth factor 2Cytotoxic therapyADC therapyClinical trialsPreclinical studiesTumor cellsTherapyTumor surface receptorsDrug conjugatesHealthy tissueFactor 2Surface receptorsTumorsTargeted deliveryDeliveryValue of Antibody Drug Conjugates for Gynecological Cancers: A Modern Appraisal Following Recent FDA Approvals
McNamara B, Chang Y, Goreshnik A, Santin A. Value of Antibody Drug Conjugates for Gynecological Cancers: A Modern Appraisal Following Recent FDA Approvals. International Journal Of Women's Health 2023, 15: 1353-1365. PMID: 37663226, PMCID: PMC10474218, DOI: 10.2147/ijwh.s400537.Peer-Reviewed Original ResearchAntibody-drug conjugatesReceptor-targeting antibodiesOngoing clinical trialsDrug conjugatesRelevant preclinical studiesRecent FDA approvalAnti-cancer therapyGynecologic malignanciesCytotoxic therapyGynecological cancerADC therapyClinical trialsPreclinical studiesFDA approvalTumor cellsTherapyHealthy tissueModern appraisalDeliveryMalignancyCancerConjugatesTrialsAntibodiesTROPiCS-03: A phase 2 basket study of sacituzumab govitecan (SG) in patients (pts) with metastatic solid tumors—Early analysis in pts with advanced/metastatic endometrial cancer (EC).
Santin A, Corr B, Spira A, Willmott L, Butrynski J, Tse K, Patel J, Mekan S, Wu T, Dumbrava E. TROPiCS-03: A phase 2 basket study of sacituzumab govitecan (SG) in patients (pts) with metastatic solid tumors—Early analysis in pts with advanced/metastatic endometrial cancer (EC). Journal Of Clinical Oncology 2023, 41: 5610-5610. DOI: 10.1200/jco.2023.41.16_suppl.5610.Peer-Reviewed Original ResearchTreatment-related adverse eventsClinical benefit rateProgression-free survivalDuration of responseWeeks of follow-upPt-based chemotherapyStable diseasePartial responseOpen-labelEndometrial cancerSafety profileFollow-upECOG PS 0-1Median duration of responseMedian progression-free survivalMedian study follow-upEC cohortAnti-PD-(L)1Metastatic solid tumorsStandard therapeutic regimensLimited treatment optionsStudy follow-upEfficacy of SGAntibody-drug conjugatesECOG PSTrastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate with topoisomerase I inhibitor payload, shows antitumor activity in uterine and ovarian carcinosarcoma with HER2/neu expression
Mauricio D, Bellone S, Mutlu L, McNamara B, Manavella D, Demirkiran C, Verzosa M, Buza N, Hui P, Hartwich T, Harold J, Yang-Hartwich Y, Zipponi M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Schwartz P, Santin A. Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate with topoisomerase I inhibitor payload, shows antitumor activity in uterine and ovarian carcinosarcoma with HER2/neu expression. Gynecologic Oncology 2023, 170: 38-45. PMID: 36610380, PMCID: PMC10445234, DOI: 10.1016/j.ygyno.2022.12.018.Peer-Reviewed Original ResearchConceptsHER2/neu expressionDS-8201aAntibody-drug conjugatesNeu expressionCS cell linesTrastuzumab deruxtecanOvarian carcinosarcomaTopoisomerase I inhibitor payloadCell linesAggressive gynecologic malignancyLimited therapeutic optionsEffective antibody-drug conjugatesCarcinosarcoma cell lineGynecologic malignanciesTherapeutic optionsIsotype controlSarcomatous elementsXenograft modelBystander killingFlow cytometryTumor cellsCarcinosarcomaAntitumor activityVivo studiesVivo activity
2022
Advances in antibody-drug conjugates for gynecologic malignancies
Tymon-Rosario J, Gorman M, Richardson D, Washington C, Santin A. Advances in antibody-drug conjugates for gynecologic malignancies. Current Opinion In Obstetrics & Gynecology 2022, 35: 6-14. PMID: 36484278, DOI: 10.1097/gco.0000000000000838.Peer-Reviewed Original ResearchConceptsAntibody-drug conjugatesOvarian cancer patientsGynecologic malignanciesCancer patientsPlatinum-resistant ovarian cancer patientsUse of ADCsOngoing phase 3 trialsRecurrent ovarian cancer patientsNovel antibody-drug conjugateReceptor-targeting antibodiesPhase 3 trialProgression-free survivalFirst U.S. FoodOngoing clinical trialsHER2/neuPersonalized cancer careTisotumab vedotinPrimary endpointCervical cancerGynecologic cancerCancer careClinical trialsMultiple tumorsCurrent evidenceDrug AdministrationTargeted Therapies in the Treatment of Uterine Serous Carcinoma
Tymon-Rosario J, Gorman M, Santin A. Targeted Therapies in the Treatment of Uterine Serous Carcinoma. Current Treatment Options In Oncology 2022, 23: 1804-1817. PMID: 36447064, DOI: 10.1007/s11864-022-01030-7.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaRecurrent diseaseSerous carcinomaTreatment of USCEffective disease-modifying treatmentMolecular classificationAppropriate surgical stagingAddition of trastuzumabCombination of immunotherapySystemic adjuvant treatmentDisease-modifying treatmentsEnrollment of patientsHER2-positive tumorsTyrosine kinase inhibitorsUnmet medical needPersonalized cancer careAntibody-drug conjugatesOpinion statementDespiteSurgical cytoreductionAdjuvant treatmentSurgical stagingDismal prognosisSurvival outcomesTherapeutic optionsCancer care
2021
Immunotherapy in Cervical Cancer
Mauricio D, Zeybek B, Tymon-Rosario J, Harold J, Santin AD. Immunotherapy in Cervical Cancer. Current Oncology Reports 2021, 23: 61. PMID: 33852056, DOI: 10.1007/s11912-021-01052-8.Peer-Reviewed Original ResearchConceptsCervical cancerDifferent immune checkpoint inhibitorsPlatinum-based chemotherapy regimenTumor-infiltrating T lymphocytesPoly adenosine diphosphate ribose polymerase inhibitorsImmune checkpoint inhibitorsCombination therapy trialsCervical cancer patientsPositive cervical cancerNovel therapeutic modalitiesRibose polymerase inhibitorsAntibody-drug conjugatesCheckpoint inhibitorsChemotherapy regimenImmunotherapy studiesTherapeutic vaccinesInvestigative treatmentCancer patientsChemotherapy treatmentT lymphocytesTherapeutic modalitiesRecent FindingsThereTumor angiogenesis inhibitorTherapy trialsAngiogenesis inhibitorsSacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial
Bardia A, Messersmith WA, Kio EA, Berlin JD, Vahdat L, Masters GA, Moroose R, Santin AD, Kalinsky K, Picozzi V, O'Shaughnessy J, Gray JE, Komiya T, Lang JM, Chang JC, Starodub A, Goldenberg DM, Sharkey RM, Maliakal P, Hong Q, Wegener WA, Goswami T, Ocean AJ. Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial. Annals Of Oncology 2021, 32: 746-756. PMID: 33741442, DOI: 10.1016/j.annonc.2021.03.005.Peer-Reviewed Original ResearchConceptsOverall safety populationAdverse eventsSacituzumab govitecanAntibody-drug conjugatesEpithelial cancersFebrile neutropeniaMost common treatment-related adverse eventsPhase I/II multicenter trialCommon treatment-related adverse eventsTreatment-related serious adverse eventsTrophoblast cell surface antigen 2Castrate-resistant prostate cancer patientsTreatment-related adverse eventsCastrate-resistant prostate cancerSmall cell lung cancerCell surface antigen 2Clinical benefit rateTreatment-related deathsObjective response rateSerious adverse eventsProgression-free survivalDuration of responseAdvanced epithelial cancersProstate cancer patientsSmall cell lungNovel mesothelin antibody-drug conjugates: current evidence and future role in the treatment of ovarian cancer
Mauricio D, Harold J, Tymon-Rosario JR, Zeybek B, Santin AD. Novel mesothelin antibody-drug conjugates: current evidence and future role in the treatment of ovarian cancer. Expert Opinion On Biological Therapy 2021, 21: 1087-1096. PMID: 33356644, DOI: 10.1080/14712598.2021.1869210.Peer-Reviewed Original ResearchConceptsAntibody-drug conjugatesOvarian cancerProgressive diseaseFavorable adverse effect profilePromising novel therapeutic agentAdverse effect profilePhase II trialDeadliest gynecologic malignancyPhase III dataNovel therapeutic agentsII trialGynecologic malignanciesEffect profileClinical resultsEffective therapyAvailable agentsCurrent evidenceNovel treatmentsChemotherapeutic agentsCancerTherapeutic agentsAdverse effectsMesothelinVivo dataDisease
2020
Novel antibody-drug conjugates: current and future roles in gynecologic oncology.
Tymon-Rosario J, Zeybek B, Santin AD. Novel antibody-drug conjugates: current and future roles in gynecologic oncology. Current Opinion In Obstetrics & Gynecology 2020, 33: 26-33. PMID: 32618744, PMCID: PMC8253558, DOI: 10.1097/gco.0000000000000642.Peer-Reviewed Original ResearchConceptsAntibody-drug conjugatesAntigen-negative cellsNovel antibody-drug conjugateAggressive gynecologic malignancyReceptor-targeting antibodiesTrop-2 overexpressionOngoing clinical trialsHER2/neuPersonalized cancer careNormal surrounding tissueAntigen-positive target cellsGynecologic malignanciesGynecologic tumorsCervical cancerSacituzumab govitecanCancer careGynecologic oncologyPreclinical dataTrastuzumab emtansineADC therapyClinical trialsMultiple tumorsCurrent standard practiceNoncleavable linkerCytotoxic moleculesSacituzumab govitecan: a promising antibody-drug conjugate for the treatment of poorly differentiated endometrial cancer
Webster EM, Zeybek B, Tymon-Rosario J, Santin AD. Sacituzumab govitecan: a promising antibody-drug conjugate for the treatment of poorly differentiated endometrial cancer. Oncoscience 2020, 7: 68-69. PMID: 33195736, PMCID: PMC7640901, DOI: 10.18632/oncoscience.514.Peer-Reviewed Original ResearchFirst-in-Human, Multicenter, Phase I Dose-Escalation and Expansion Study of Anti-Mesothelin Antibody–Drug Conjugate Anetumab Ravtansine in Advanced or Metastatic Solid Tumors
Hassan R, Blumenschein GR, Moore KN, Santin AD, Kindler HL, Nemunaitis JJ, Seward SM, Thomas A, Kim SK, Rajagopalan P, Walter AO, Laurent D, Childs BH, Sarapa N, Elbi C, Bendell JC. First-in-Human, Multicenter, Phase I Dose-Escalation and Expansion Study of Anti-Mesothelin Antibody–Drug Conjugate Anetumab Ravtansine in Advanced or Metastatic Solid Tumors. Journal Of Clinical Oncology 2020, 38: 1824-1835. PMID: 32213105, PMCID: PMC7255978, DOI: 10.1200/jco.19.02085.Peer-Reviewed Original ResearchConceptsAnetumab ravtansineDose-escalation cohortsMetastatic solid tumorsAnti-mesothelin antibodySolid tumorsExpansion cohortClinical activityCommon drug-related adverse eventsDrug-related adverse eventsPhase I Dose-EscalationMultiple solid tumor typesPhase IDose-expansion studyI Dose-EscalationPeripheral sensory neuropathyPhase II studyRecurrent ovarian cancerRecurrent solid tumorsPreliminary antitumor activityDrug-related deathsFavorable pharmacokinetic profileSolid tumor typesAntibody-drug conjugatesStable diseaseAdult patientsCervical carcinomas that overexpress human trophoblast cell-surface marker (Trop-2) are highly sensitive to the antibody-drug conjugate sacituzumab govitecan
Zeybek B, Manzano A, Bianchi A, Bonazzoli E, Bellone S, Buza N, Hui P, Lopez S, Perrone E, Manara P, Zammataro L, Altwerger G, Han C, Tymon-Rosario J, Menderes G, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Santin A. Cervical carcinomas that overexpress human trophoblast cell-surface marker (Trop-2) are highly sensitive to the antibody-drug conjugate sacituzumab govitecan. Scientific Reports 2020, 10: 973. PMID: 31969666, PMCID: PMC6976591, DOI: 10.1038/s41598-020-58009-3.Peer-Reviewed Original ResearchConceptsSquamous cell carcinomaSacituzumab govitecanTrop-2 expressionAntibody-drug conjugatesCell surface markersXenograft modelTrop-2Adenocarcinoma/adenosquamous carcinomaAnti-Trop-2 antibodyCell linesWeekly intravenous administrationSignificant tumor growth inhibitionCervical cancer patientsPrimary cervical cancerStrong diffuse stainingPrimary cervical tumorsCervical cancer cell linesEpithelial solid tumorsReal-time polymerase chain reactionTumor growth inhibitionHuman placental tissuePositive cell linesNegative cell linesVivo antitumor activityCancer cell lines
2019
93 Sacituzumab govitecan in uterine and ovarian carcinosarcomas
Lopez S, Perrone E, Zeybek B, Bellone S, Manzano A, Zammataro L, Han C, Altwerger G, Angioli R, Santin A. 93 Sacituzumab govitecan in uterine and ovarian carcinosarcomas. International Journal Of Gynecological Cancer 2019, 29: a48. DOI: 10.1136/ijgc-2019-igcs.93.Peer-Reviewed Original ResearchCS cell linesAntibody-drug conjugatesSacituzumab govitecanTrop-2 expressionTrop-2Negative tumorsCell linesControl antibody drug conjugatesNovel antibody-drug conjugateAggressive gynecologic malignancyGreater antitumor effectPrimary tumor cell linesRemarkable antitumor activityAggressive carcinosarcomasGynecologic malignanciesOvarian carcinosarcomaPrimary tumorClinical trialsEpithelial tumorsSarcomatous elementsAntitumor effectsAntigen 2CarcinosarcomaActive metaboliteSN-38Cervical carcinomas that overexpress human trophoblast cell-surface marker (Trop-2) are highly sensitive to the antibody-drug conjugate sacituzumab govitecan.
Zeybek B, Manzano A, Bianchi A, Bonazzoli E, Buza N, Lopez S, Perrone E, Manara P, Bellone S, Zammataro L, Santin A. Cervical carcinomas that overexpress human trophoblast cell-surface marker (Trop-2) are highly sensitive to the antibody-drug conjugate sacituzumab govitecan. Journal Of Clinical Oncology 2019, 37: e17028-e17028. DOI: 10.1200/jco.2019.37.15_suppl.e17028.Peer-Reviewed Original ResearchSquamous cell carcinomaPrimary cervical cancer cell linesControl antibody drug conjugatesAntibody-drug conjugatesIMMU-132Clear cell carcinomaTrop-2 expressionCervical cancer cell linesCell carcinomaCancer cell linesCervical cancerSacituzumab govitecanNeuroendocrine carcinomaCervical tumorsCell linesTrop-2Cervical cancer cell viabilityNaked antibodiesWeekly intravenous administrationSignificant tumor growth inhibitionStrong diffuse stainingUnmet medical needPrimary tumor cell linesReal-time polymerase chain reactionTumor growth inhibition
2018
Sacituzumab 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
2017
SYD985, a Novel Duocarmycin-Based HER2-Targeting Antibody–Drug Conjugate, Shows Antitumor Activity in Uterine and Ovarian Carcinosarcoma with HER2/Neu Expression
Menderes G, Bonazzoli E, Bellone S, Black J, Predolini F, Pettinella F, Masserdotti A, Zammataro L, Altwerger G, Buza N, Hui P, Wong S, Litkouhi B, Ratner E, Silasi DA, Azodi M, Schwartz PE, Santin AD. SYD985, a Novel Duocarmycin-Based HER2-Targeting Antibody–Drug Conjugate, Shows Antitumor Activity in Uterine and Ovarian Carcinosarcoma with HER2/Neu Expression. Clinical Cancer Research 2017, 23: 5836-5845. PMID: 28679774, PMCID: PMC5626613, DOI: 10.1158/1078-0432.ccr-16-2862.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAnimalsAntibody-Dependent Cell CytotoxicityCarcinosarcomaCell Line, TumorCell ProliferationDuocarmycinsFemaleGene Expression Regulation, NeoplasticHumansImmunoconjugatesIndolesMaytansineMiceOvarian NeoplasmsPyrrolidinonesReceptor, ErbB-2TrastuzumabUterine NeoplasmsXenograft Model Antitumor AssaysConceptsAntibody-dependent cellular cytotoxicityHER2/neu expressionHER2/neu 3T-DM1Antibody-drug conjugatesCS cell linesNeu expressionEffector cellsHigh HER2/neu expressionNeu 3HER2-targeting antibody-drug conjugateCell linesBystander killingPatient-derived xenograft modelsNovel HER2-targeting antibody-drug conjugateAggressive gynecologic malignancyHigh HER2 expressionEffective antibody-drug conjugatesHER2/neuClin Cancer ResGynecologic malignanciesOvarian carcinosarcomaHER2 expressionTrastuzumab emtansineSYD985