2024
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
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. 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 ratePatients
2023
In Vivo and In Vitro Efficacy of Trastuzumab Deruxtecan in Uterine Serous Carcinoma.
Mutlu L, Manavella D, Bellone S, McNamara B, Harold J, Mauricio D, Siegel E, Buza N, Hui P, Hartwich T, Yang-Hartwich Y, Demirkiran C, Verzosa M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Dottino P, Schwartz P, Santin A. In Vivo and In Vitro Efficacy of Trastuzumab Deruxtecan in Uterine Serous Carcinoma. Molecular Cancer Therapeutics 2023, 22: 1404-1412. PMID: 37676984, DOI: 10.1158/1535-7163.mct-23-0126.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaAntibody-dependent cellular cytotoxicityT-DXdUSC patientsUSC cell linesTrastuzumab deruxtecanSerous carcinomaHER2 expressionClinical trialsRecurrent uterine serous carcinomaTopoisomerase I inhibitor payloadSignificant antibody-dependent cellular cytotoxicityCell linesMultiple tumor indicationsPrimary USC cell linesLow HER2 expressionFuture clinical trialsHigh recurrence ratePeripheral blood lymphocytesERBB2 gene amplificationGrowth suppressionHER2-overexpressing cell linesTumor growth suppressionOverall survivalStandard chemotherapyUterine leiomyosarcomas harboring MAP2K4 gene amplification are sensitive in vivo to PLX8725, a novel MAP2K4 inhibitor
McNamara B, Harold J, Manavella D, Bellone S, Mutlu L, Hartwich T, Zipponi M, Yang-Hartwich Y, Demirkiran C, Verzosa M, Yang K, Choi J, Dong W, Buza N, Hui P, Altwerger G, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Burton E, Inagaki H, Albers A, Zhang C, Bollag G, Schlessinger J, Santin A. Uterine leiomyosarcomas harboring MAP2K4 gene amplification are sensitive in vivo to PLX8725, a novel MAP2K4 inhibitor. Gynecologic Oncology 2023, 172: 65-71. PMID: 36958197, PMCID: PMC10192120, DOI: 10.1016/j.ygyno.2023.03.009.Peer-Reviewed Original ResearchConceptsUterine leiomyosarcomaPDX modelsGain of functionMedian overall survivalPhase I trialOral gavage dailyVivo activityTumor growth inhibitionTumor volume differencesTumor cell proliferationOverall survivalTolerable toxicityI trialOral treatmentTreatment cohortsGavage dailyAggressive tumorsSCID miceULMS patientsPK studiesTumor samplesWestern blotCell proliferationControl vehicleLeiomyosarcoma
2022
Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma
Harold J, Bellone S, Manavella D, Mutlu L, McNamara B, Hartwich T, Zipponi M, Yang-Hartwich Y, Demirkiran C, Verzosa M, Choi J, Dong W, Buza N, Hui P, Altwerger G, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Santin A. Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma. Gynecologic Oncology 2022, 168: 157-165. PMID: 36442427, PMCID: PMC9797429, DOI: 10.1016/j.ygyno.2022.11.014.Peer-Reviewed Original ResearchConceptsPatient-derived xenograftsUterine leiomyosarcomaVivo activityVehicle control treatmentMedian overall survivalTumor volume differencesOral scheduleWestern blot analysisOverall survivalOral gavageAggressive malignancyPDX modelsClinical trialsSCID miceTumor measurementsULMS patientsSignificant growth inhibitionNovel ATR inhibitorTumor samplesSignificant toxicityWestern blotKinase inhibitorsATRX mutationsGene mutationsControl vehicle
2021
A 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 MSIPrognostic impact of mismatch repair deficiency in high- and low-intermediate-risk, early-stage endometrial cancer following vaginal brachytherapy
Li JY, Park HS, Huang GS, Young MR, Ratner E, Santin A, Damast S. Prognostic impact of mismatch repair deficiency in high- and low-intermediate-risk, early-stage endometrial cancer following vaginal brachytherapy. Gynecologic Oncology 2021, 163: 557-562. PMID: 34602287, DOI: 10.1016/j.ygyno.2021.09.018.Peer-Reviewed Original ResearchConceptsRecurrence-free survivalEndometrioid endometrial cancerVaginal brachytherapyPMMR patientsOverall survivalEEC patientsEndometrial cancerExact testThree-year recurrence-free survivalEarly-stage endometrial cancerCox proportional hazards regressionPoor recurrence-free survivalAdjuvant vaginal brachytherapyThree-year OSMultivariable Cox regressionLympho-vascular invasionSignificant prognostic variablesProportional hazards regressionLog-rank testKaplan-Meier estimatesDeficient mismatch repairMismatch repair statusFisher's exact testMismatch repair deficiencyDMMR status
2020
Stage 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 samplingPreclinical activity of sacituzumab govitecan (IMMU-132) in uterine and ovarian carcinosarcomas
Lopez S, Perrone E, Bellone S, Bonazzoli E, Zeybek B, Han C, Tymon-Rosario J, Altwerger G, Menderes G, Bianchi A, Zammataro L, Manzano A, Manara P, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Raspagliesi F, Angioli R, Buza N, Hui P, Bond HM, Santin AD. Preclinical activity of sacituzumab govitecan (IMMU-132) in uterine and ovarian carcinosarcomas. Oncotarget 2020, 11: 560-570. PMID: 32082489, PMCID: PMC7007291, DOI: 10.18632/oncotarget.27342.Peer-Reviewed Original ResearchSacituzumab govitecanTrop-2 expressionTrop-2Ovarian carcinosarcomaWeekly intravenous administrationSignificant tumor growth inhibitionTumor growth inhibitionCS cell linesCell linesCell surface markersNegative cell linesAggressive carcinosarcomasCarcinosarcoma patientsPrimary carcinosarcomaOverall survivalPoor prognosisPreclinical activityRare cancersIntravenous administrationXenograft modelActive drugCarcinosarcomaActive metaboliteFFPE tumorsCell viability assays
2019
Neutrophilia and mortality in women with uterine carcinosarcoma
Arend R, Van Arsdale A, Gojayev A, Roane BM, Doo D, Leath C, Goldberg GL, Huang G. Neutrophilia and mortality in women with uterine carcinosarcoma. International Journal Of Gynecological Cancer 2019, 29: 1258. PMID: 31320488, DOI: 10.1136/ijgc-2019-000440.Peer-Reviewed Original ResearchConceptsPre-treatment absolute neutrophil countAbsolute neutrophil countIndependent poor prognostic factorProgression-free survivalPoor prognostic factorNeutrophil countUterine carcinosarcomaOverall survivalPrognostic factorsMultivariable Cox proportional hazards regression modelsCox proportional hazards regression modelAbsolute neutrophil count dataHigher absolute neutrophil countKaplan-Meier survival estimatesProportional hazards regression modelsUterine carcinosarcoma patientsRetrospective cohort studyHazards regression modelsLog-rank testInstitutional review boardCarcinosarcoma patientsCohort studyDisease recurrenceClinical outcomesHighest quartile
2018
Impact of carboplatin hypersensitivity and desensitization on patients with recurrent ovarian cancer
Altwerger G, Florsheim EB, Menderes G, Black J, Schwab C, Gressel GM, Nelson WK, Carusillo N, Passante T, Huang G, Litkouhi B, Azodi M, Silasi DA, Santin A, Schwartz PE, Ratner ES. Impact of carboplatin hypersensitivity and desensitization on patients with recurrent ovarian cancer. Journal Of Cancer Research And Clinical Oncology 2018, 144: 2449-2456. PMID: 30255380, DOI: 10.1007/s00432-018-2753-y.Peer-Reviewed Original ResearchConceptsCarboplatin hypersensitivityCarboplatin desensitizationHypersensitive patientsOverall survivalRisk factorsOvarian cancerTwo-sided Fisher exactAdvanced stage ovarian cancerInfusion of carboplatinRecurrent ovarian cancerIndependent risk factorLonger overall survivalStage ovarian cancerOvarian cancer patientsLong-term treatmentNew risk factorsHigher likelihoodTwo-sided p valueT-testStudent's t-testDesignRetrospective studyGermline BRCA1/2Improved OSLonger OSDesensitization protocolInsulin‐like growth factor 2: a poor prognostic biomarker linked to racial disparity in women with uterine carcinosarcoma
Van Arsdale AR, Arend RC, Cossio MJ, Erickson BK, Wang Y, Doo DW, Leath CA, Goldberg GL, Huang GS. Insulin‐like growth factor 2: a poor prognostic biomarker linked to racial disparity in women with uterine carcinosarcoma. Cancer Medicine 2018, 7: 616-625. PMID: 29455465, PMCID: PMC5852335, DOI: 10.1002/cam4.1335.Peer-Reviewed Original ResearchConceptsProgression-free survivalOverall survivalUterine carcinosarcomaHigh IGF2IGF2 levelsMultivariable Cox proportional hazards regression modelsCox proportional hazards regression modelRace-stratified multivariable analysesProportional hazards regression modelsReduced progression-free survivalInsulin-like growth factor 2 expressionRacial disparitiesIndependent risk factorEarly-stage diseaseRisk of deathHazards regression modelsPoor prognostic biomarkerGrowth factor 2 expressionFactor 2 (Nrf2) protein expressionFactor 2 expressionBlack womenAdjuvant therapyWhite patientsMultivariable analysisBlack race
2009
A phase II study of weekly topotecan and docetaxel in heavily treated patients with recurrent uterine and ovarian cancers
Gupta D, Owers RL, Kim M, Kuo DY, Huang GS, Shahabi S, Goldberg GL, Einstein MH. A phase II study of weekly topotecan and docetaxel in heavily treated patients with recurrent uterine and ovarian cancers. Gynecologic Oncology 2009, 113: 327-330. PMID: 19307014, PMCID: PMC4451225, DOI: 10.1016/j.ygyno.2009.02.018.Peer-Reviewed Original ResearchConceptsWeekly topotecanClinical benefitOverall survivalOvarian cancerGrade 3 non-hematologic toxicityKaplan-Meier statistical methodNon-hematologic toxicitiesPrior chemotherapy regimensCycles of chemotherapyGrade 3 toxicityMedian overall survivalPhase II studyPhase II trialMajority of patientsEpithelial ovarian cancerOverall response ratePlatinum-resistant tumorsDose delaysEligible patientsRustin criteriaChemotherapy regimensII trialUnacceptable toxicityII studyMedian duration
2005
Consolidation therapy for ovarian cancer
Huang G, Goldberg G, Fields A. Consolidation therapy for ovarian cancer. The Women's Oncology Review 2005, 5: 3-8. DOI: 10.3109/14733400500070708.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsWhole abdominal radiotherapyConsolidation therapyOvarian cancerCatheter-related complicationsRecurrence-free intervalLate radiation toxicityConsolidation regimensPaclitaxel therapyOverall survivalSurvival benefitBiologic agentsRandomized studyCA 125Randomized trialsRadiation toxicityMEDLINE searchTherapyCancerToxic agentsClinical acceptanceRadiotherapyInternational meetingsRegimensChemotherapyComplications