2024
Randomized phase II trial of weekly ixabepilone with or without biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer: Updated survival and subgroup analyses
Roque D, Siegel E, Buza N, Bellone S, Huang G, Andikyan V, Clark M, Azodi M, Schwartz P, Rao G, Xu F, Hui P, Altwerger G, Ratner E, Santin A. Randomized phase II trial of weekly ixabepilone with or without biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer: Updated survival and subgroup analyses. Gynecologic Oncology 2024, 190: s299-s301. DOI: 10.1016/j.ygyno.2024.07.449.Peer-Reviewed Original ResearchPre-clinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition for low-grade serous ovarian cancer
McNamara B, Greenman M, Demirkiran C, Mutlu L, Hartwich T, Bellone S, Manavella D, Zipponi M, Yang-Hartwich Y, Yang K, Ratner E, Schwartz P, Santin A. Pre-clinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition for low-grade serous ovarian cancer. Gynecologic Oncology 2024, 190: s36. DOI: 10.1016/j.ygyno.2024.07.058.Peer-Reviewed Original ResearchEV016/#559 Preclinical activity of datopotamab deruxtecan, a novel trophoblast cell-surface antigen 2 (TROP2) directed antibody-drug conjugate targeting TROP2 in high grade serous ovarian carcinoma
Mcnamara B, Greenman M, Bellone S, Demirkiran C, Mutlu L, Hartwich T, Yang-Hartwich Y, Ratner E, Schwartz P, Santin A. EV016/#559 Preclinical activity of datopotamab deruxtecan, a novel trophoblast cell-surface antigen 2 (TROP2) directed antibody-drug conjugate targeting TROP2 in high grade serous ovarian carcinoma. 2024, a91.2-a91. DOI: 10.1136/ijgc-2024-igcs.135.Peer-Reviewed Original ResearchPreclinical activity of datopotamab deruxtecan, a novel TROP2 directed antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (TROP2) in ovarian carcinoma
McNamara B, Greenman M, Bellone S, Santin L, Demirkiran C, Mutlu L, Hartwich T, Yang-Hartwich Y, Ratner E, Schwartz P, Santin A. Preclinical activity of datopotamab deruxtecan, a novel TROP2 directed antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (TROP2) in ovarian carcinoma. Gynecologic Oncology 2024, 189: 16-23. PMID: 38981151, DOI: 10.1016/j.ygyno.2024.07.002.Peer-Reviewed Original ResearchTargets trophoblast cell-surface antigen-2Epithelial ovarian cancerAntibody-dependent cellular cytotoxicityPreclinical activityAntibody drug conjugatesOvarian cancerCell linesTumor cellsTrophoblast cell surface antigen 2Cell line-derived xenograft modelFlow cytometryCompared to tumor cellsEpithelial ovarian cancer cell linesOvarian cancer cell linesTumor cells in vitroOvarian cancer patientsPeripheral-blood lymphocytesEOC cell linesTumor growth suppressionAnnexin V-positiveGynecologic cancer mortalityIn vivo antitumor activityCells in vitroPrimary cell linesUnmet medical needTrastuzumab 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 cancerRandomized phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer (NCT03093155): Updated survival and subgroup analyses
Roque D, Siegel E, Buza N, Bellone S, Huang G, Altwerger G, Andikyan V, Clark M, Azodi M, Schwartz P, Rao G, Ratner E, Santin A. Randomized phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer (NCT03093155): Updated survival and subgroup analyses. BJC Reports 2024, 2: 43. PMID: 39516558, PMCID: PMC11523995, DOI: 10.1038/s44276-024-00067-5.Peer-Reviewed Original ResearchPre-treated ovarian cancerOverall survivalBev armsDose reductionOvarian cancerTaxane responseRandomized phase 2 trialRandomized phase II trialPaclitaxel-resistant diseaseResultsThirty-seven patientsTreated with paclitaxelPhase 2 trialBiweekly bevacizumabDays 1,8,15Taxane-sensitiveUpdate survivalProgression-freePeritoneal cancerDose modificationTaxane sensitivityPlatinum resistanceSubset analysisSubgroup analysisResponse ratePatientsPreclinical in vitro and in vivo activity of the RAF/MEK clamp avutometinib in combination with FAK inhibition in uterine carcinosarcomas
Demirkiran C, Greenman M, Bellone S, McNamara B, Hartwich T, Manavella D, Mutlu L, Zipponi M, Yang-Hartwich Y, Yang K, Ratner E, Schwartz P, Coma S, Pachter J, Santin A. Preclinical in vitro and in vivo activity of the RAF/MEK clamp avutometinib in combination with FAK inhibition in uterine carcinosarcomas. Gynecologic Oncology 2024, 187: 12-20. PMID: 38703673, DOI: 10.1016/j.ygyno.2024.04.010.Peer-Reviewed Original ResearchFocal adhesion kinaseUC cell linesWhole-exome-sequencingFAK inhibitorCell linesFocal adhesion kinase inhibitionPhosphorylated (p)‑FAKWestern blot assayRAF/MEK inhibitionUterine carcinosarcomaRAS/MAPK pathway genesPreclinical in vitroBlot assayVS-4718Cell cycle assayGenetic landscapePathway genesMAP2KGenetic alterationsDecreased p-ERKCycle assaySuperior tumor growth inhibitionBiologically aggressive tumorsGrowth inhibitionIn vitro activityIntegrated mutational landscape analysis of poorly differentiated high-grade neuroendocrine carcinoma of the uterine cervix
Bellone S, Jeong K, Halle M, Krakstad C, McNamara B, Greenman M, Mutlu L, Demirkiran C, Hartwich T, Yang-Hartwich Y, Zipponi M, Buza N, Hui P, Raspagliesi F, Lopez S, Paolini B, Milione M, Perrone E, Scambia G, Altwerger G, Ravaggi A, Bignotti E, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Quick C, Angioli R, Terranova C, Zaidi S, Nandi S, Alexandrov L, Siegel E, Choi J, Schlessinger J, Santin A. Integrated mutational landscape analysis of poorly differentiated high-grade neuroendocrine carcinoma of the uterine cervix. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2321898121. PMID: 38625939, PMCID: PMC11046577, DOI: 10.1073/pnas.2321898121.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingPatient-derived-xenograftsBase excision repairCopy number lossMultiregion whole-exome sequencingCopy number gainHigh-grade neuroendocrine carcinomaCNV analysisPhylogenetic analysisEvolutionary historyNeuroendocrine cervical cancerHuman papillomavirus DNAMutator phenotypeSensitivity to afatinibGenetic landscapeRecurrent mutationsRNA sequencingGene fusionsMutational landscape analysisExcision repairGenesMutationsPan-HERConsistent with deficiencyNeuroendocrine carcinomaRandomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147)
Sheth S, Oh J, Bellone S, Siegel E, Greenman M, Mutlu L, McNamara B, Pathy S, Clark M, Azodi M, Altwerger G, Andikyan V, Huang G, Ratner E, Kim D, Iwasaki A, Levi A, Buza N, Hui P, Flaherty S, Schwartz P, Santin A. Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147). Clinical Cancer Research 2024, 30: of1-of10. PMID: 38592381, DOI: 10.1158/1078-0432.ccr-23-3639.Peer-Reviewed Original ResearchConceptsRandomized phase II trialCD4/CD8 T cellsT cellsHPV clearanceArm BNo significant differenceClinical surveillanceRate of HPV clearanceSecondary outcomesPre-neoplastic cervical lesionsCervical intraepithelial neoplasiaT cell infiltrationT cell responsesSignificant differenceCIN3 patientsIntraepithelial neoplasiaArm ACervical lesionsImiquimod groupSurveillance armVaginal suppositoriesProspective trialsArm CHPV vaccinationImiquimodPreclinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition in low grade serous ovarian cancer
McNamara B, Demirkiran C, Hartwich T, Bellone S, Manavella D, Mutlu L, Greenman M, Zipponi M, Yang-Hartwich Y, Yang K, Ratner E, Schwartz P, Coma S, Pachter J, Santin A. Preclinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition in low grade serous ovarian cancer. Gynecologic Oncology 2024, 183: 133-140. PMID: 38493021, DOI: 10.1016/j.ygyno.2024.01.028.Peer-Reviewed Original ResearchLow grade serous ovarian carcinomaWhole-exome-sequencingGain-of-function mutationsVS-4718Preclinical efficacyLow grade serous ovarian cancerSerous ovarian cancerControl-treated miceTumor growth inhibitionWild-type KRASLoss of heterozygosityDecreased p-ERKRAF/MEK inhibitionMedian survivalOvarian cancerRecurrence rateTherapeutic optionsOral gavageTumor growthTumor samplesIn vivo activityMAPK pathway genesRAF/MEK inhibitorsP-ERKEx vivoCorrection: Randomised phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer
Roque D, Siegel E, Buza N, Bellone S, Silasi D, Huang G, Andikyan V, Clark M, Azodi M, Schwartz P, Rao G, Reader J, Hui P, Tymon-Rosario J, Harold J, Mauricio D, Zeybek B, Menderes G, Altwerger G, Ratner E, Santin A. Correction: Randomised phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer. British Journal Of Cancer 2024, 130: 1073-1073. PMID: 38438590, PMCID: PMC10951353, DOI: 10.1038/s41416-024-02628-4.Peer-Reviewed Original Research
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 agentHomologous recombination deficiency (HRD) signature-3 in ovarian and uterine carcinosarcomas correlates with preclinical sensitivity to Olaparib, a poly (adenosine diphosphate [ADP]- ribose) polymerase (PARP) inhibitor
Tymon-Rosario JR, Manara P, Manavella DD, Bellone S, Hartwich TMP, Harold J, Yang-Hartwich Y, Zipponi M, Choi J, Jeong K, Mutlu L, Yang K, Altwerger G, Menderes G, Ratner E, Huang GS, Clark M, Andikyan V, Azodi M, Schwartz PE, Alexandrov LB, Santin AD. Homologous recombination deficiency (HRD) signature-3 in ovarian and uterine carcinosarcomas correlates with preclinical sensitivity to Olaparib, a poly (adenosine diphosphate [ADP]- ribose) polymerase (PARP) inhibitor. Gynecologic Oncology 2022, 166: 117-125. PMID: 35599167, DOI: 10.1016/j.ygyno.2022.05.005.Peer-Reviewed Original ResearchConceptsUterine carcinosarcomaCS cell linesSignature 3Cell linesPolymerase inhibitorsOverall animal survivalFresh tumor samplesPoly (ADP-ribose) polymerase (PARP) inhibitorsXenograft tumor growthG2/M phaseAggressive malignancyCS patientsPrimary tumorCell cycle arrestPrimary cell linesPoor survivalClinical studiesPreclinical sensitivityCarcinosarcomaTumor growthAnimal survivalOlaparib activityTumor samplesOlaparibAntitumor activityEffect of exercise on body composition among women with ovarian cancer
Cao A, Cartmel B, Li FY, Gottlieb LT, Harrigan M, Ligibel JA, Gogoi R, Schwartz PE, Irwin ML, Ferrucci LM. Effect of exercise on body composition among women with ovarian cancer. Journal Of Cancer Survivorship 2022, 17: 1386-1396. PMID: 35377104, PMCID: PMC9530065, DOI: 10.1007/s11764-022-01207-x.Peer-Reviewed Original ResearchConceptsDual-energy X-ray absorptiometryOvarian cancer survivorsAerobic exercise interventionEffects of exerciseCancer survivorsOvarian cancerExercise interventionBody compositionSix-month aerobic exercise interventionBone mineral densityBetween-group differencesBody fat percentageLean body massX-ray absorptiometrySecondary outcomesStudy armsAerobic exerciseLifestyle StudyMineral densityHigh riskCancerSurvivorsFat percentageWomenResultsOn averageSafety Warning about Laparoscopic Power Morcellation in Hysterectomy: A Cost-Effectiveness Analysis of National Impact
Xu X, Desai VB, Schwartz PE, Gross CP, Lin H, Schymura MJ, Wright JD. Safety Warning about Laparoscopic Power Morcellation in Hysterectomy: A Cost-Effectiveness Analysis of National Impact. Women's Health Reports 2022, 3: 369-384. PMID: 35415718, PMCID: PMC8994439, DOI: 10.1089/whr.2021.0101.Peer-Reviewed Original ResearchAn evaluation of prognostic factors, oncologic outcomes, and management for primary and recurrent squamous cell carcinoma of the vulva
Li JY, Arkfeld CK, Tymon-Rosario J, Webster E, Schwartz P, Damast S, Menderes G. An evaluation of prognostic factors, oncologic outcomes, and management for primary and recurrent squamous cell carcinoma of the vulva. Journal Of Gynecologic Oncology 2022, 33: 0. PMID: 34910394, PMCID: PMC8899873, DOI: 10.3802/jgo.2022.33.e13.Peer-Reviewed Original ResearchConceptsDisease-specific survivalSquamous cell carcinomaOverall survivalPositive marginsCell carcinomaNodal involvementPrognostic factorsStage IFive-year disease-specific survivalPrimary squamous cell carcinomaRecurrent squamous cell carcinomaFive-year RFSNode-positive patientsVulvar cancer patientsEscalation of treatmentConservative surgical approachKaplan-Meier estimatesLog-rank testCox proportional hazardsLocal RFSOverall RFSAdjuvant radiotherapyDistant recurrenceFree survivalMedian survivalRandomised phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer
Roque DM, Siegel ER, Buza N, Bellone S, Silasi DA, Huang GS, Andikyan V, Clark M, Azodi M, Schwartz PE, Rao GG, Reader JC, Hui P, Tymon-Rosario JR, Harold J, Mauricio D, Zeybek B, Menderes G, Altwerger G, Ratner E, Santin AD. Randomised phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer. British Journal Of Cancer 2022, 126: 1695-1703. PMID: 35149854, PMCID: PMC8853032, DOI: 10.1038/s41416-022-01717-6.Peer-Reviewed Original ResearchConceptsPrimary peritoneal cancerPeritoneal cancerPredictive biomarkersDay 1Taxane-resistant ovarian cancerPhase II trialM2 days 1Bevacizumab 10Evaluable patientsPrior bevacizumabWeekly ixabepiloneII trialPrimary endpointSecondary endpointsRefractory statusTUBB3 expressionPrior receiptSubgroup analysisClinical trialsOvarian cancerIxabepilonePFSCancerBevacizumabPatients
2021
Clinicopathologic characteristics and oncologic outcomes in adenosarcoma of gynecologic sites
Li JY, Mutlu L, Tymon-Rosario J, Khadraoui W, Nagarkatti N, Hui P, Buza N, Lu L, Schwartz P, Menderes G. Clinicopathologic characteristics and oncologic outcomes in adenosarcoma of gynecologic sites. Gynecologic Oncology Reports 2021, 39: 100913. PMID: 35005157, PMCID: PMC8715286, DOI: 10.1016/j.gore.2021.100913.Peer-Reviewed Original ResearchRecurrence-free survivalEarly-stage diseaseHigh-grade histologyOvarian preservationNode dissectionGrade histologyOncologic outcomesOverall survivalClinicopathologic characteristicsMyometrial invasionSarcomatous overgrowthPatients underwent lymph node dissectionUnderwent lymph node dissectionCox proportional hazards regressionLymph node dissectionEvidence of diseaseNon-inferior outcomesDeep myometrial invasionProportional hazards regressionLog-rank testKaplan-Meier estimatesLarge patient cohortPractical management optionsBilateral adnexectomyCervical adenosarcomaA phase 2 evaluation of pembrolizumab for recurrent Lynch‐like versus sporadic endometrial cancers with microsatellite instability
Bellone S, Roque DM, Siegel ER, Buza N, Hui P, Bonazzoli E, Guglielmi A, Zammataro L, Nagarkatti N, Zaidi S, Lee J, Silasi D, Huang GS, Andikyan V, Damast S, Clark M, Azodi M, Schwartz PE, Tymon‐Rosario J, Harold JA, Mauricio D, Zeybek B, Menderes G, Altwerger G, Ratner E, Alexandrov LB, Iwasaki A, Kong Y, Song E, Dong W, Elvin JA, Choi J, Santin AD. A phase 2 evaluation of pembrolizumab for recurrent Lynch‐like versus sporadic endometrial cancers with microsatellite instability. Cancer 2021, 128: 1206-1218. PMID: 34875107, PMCID: PMC9465822, DOI: 10.1002/cncr.34025.Peer-Reviewed Original ResearchConceptsObjective response rateImmune checkpoint inhibitorsProgression-free survivalEndometrial cancerWhole-exome sequencingSporadic endometrial cancerOverall survivalEnd pointPhase 2 pilot studyPrimary end pointSecondary end pointsTumor mutation burdenPhase 2 evaluationLarger confirmatory studiesAntigen processing/presentationProcessing/presentationCheckpoint inhibitorsSurgical resectionICI resistanceDMMR patientsPrognostic significanceDMMR tumorsMechanisms of resistanceLocal treatmentSporadic MSIProgression of Cystadenoma to Mucinous Borderline Ovarian Tumor in Young Females: Case Series and Literature Review
Beroukhim G, Ozgediz D, Cohen PJ, Hui P, Morotti R, Schwartz PE, Yang-Hartwich, Vash-Margita A. Progression of Cystadenoma to Mucinous Borderline Ovarian Tumor in Young Females: Case Series and Literature Review. Journal Of Pediatric And Adolescent Gynecology 2021, 35: 359-367. PMID: 34843973, DOI: 10.1016/j.jpag.2021.11.003.Peer-Reviewed Original ResearchConceptsMucinous borderline ovarian tumorsBorderline ovarian tumorsOvarian tumorsYale-New Haven HospitalRetrospective chart reviewBenign ovarian tumorsBenign ovarian lesionsRate of recurrenceNew Haven HospitalAbdominal painPreoperative characteristicsChart reviewDisease recurrenceRecurrent cystsCase seriesChief complaintClinical presentationClinicopathologic featuresFemale patientsMucinous cystadenomaOvarian cystsOvarian lesionsTumor stageAdolescent patientsSubsequent surveillance