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 chemotherapyTrastuzumab deruxtecan in recurrent uterine serous carcinoma resistant to trastuzmab based-chemotherapy
McNamara B, Bellone S, Demirkiran C, Hartwich T, Santin A. Trastuzumab deruxtecan in recurrent uterine serous carcinoma resistant to trastuzmab based-chemotherapy. Gynecologic Oncology Reports 2023, 48: 101219. PMID: 37325293, PMCID: PMC10265462, DOI: 10.1016/j.gore.2023.101219.Peer-Reviewed Original ResearchUterine serous carcinomaHER2/neuSerous carcinomaT-DXdTreatment optionsRecurrent uterine serous carcinomaDose-limiting side effectEffective treatment optionNew treatment optionsBone painRecurrent diseaseDurable responsesTrastuzumab deruxtecanCA 125Disease burdenSide effectsCarcinomaAntibody drugsTreatmentSignificant reductionDiseaseNeuExperimental treatmentsMetastaticPainPreliminary results of a phase II trial with sacituzumab govitecan-hziy in patients with recurrent endometrial carcinoma overexpressing Trop-2.
Santin A, McNamara B, Siegel E, Harold J, Mutlu L, Altwerger G, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Dottino P, Schwartz P, Bellone S. Preliminary results of a phase II trial with sacituzumab govitecan-hziy in patients with recurrent endometrial carcinoma overexpressing Trop-2. Journal Of Clinical Oncology 2023, 41: 5599-5599. DOI: 10.1200/jco.2023.41.16_suppl.5599.Peer-Reviewed Original ResearchRecurrent endometrial carcinomaSacituzumab govitecan-hziyTrop-2 overexpressionPhase 2 trialEndometrial carcinomaUterine serous carcinomaTrop-2Endometrioid adenocarcinomaSerous carcinomaClinical activityMetastatic triple-negative breast cancerAnti-Trop-2 antibodyGrade 3 endometrioid adenocarcinomaTriple-negative breast cancerAdequate bone marrowUnexpected safety signalsMetastatic urothelial cancerClear cell histologyPhase II trialSystemic corticosteroid usePlatinum-based chemotherapyFavorable safety profileDurable disease controlRemarkable clinical activityStage 1Monitoring Treatment Response, Early Recurrence, and Survival in Uterine Serous Carcinoma and Carcinosarcoma Patients Using Personalized Circulating Tumor DNA Biomarkers
Bellone S, McNamara B, Mutlu L, Demirkiran C, Hartwich T, Harold J, Yang-Hartwich Y, Siegel E, Santin A. Monitoring Treatment Response, Early Recurrence, and Survival in Uterine Serous Carcinoma and Carcinosarcoma Patients Using Personalized Circulating Tumor DNA Biomarkers. International Journal Of Molecular Sciences 2023, 24: 8873. PMID: 37240216, PMCID: PMC10219151, DOI: 10.3390/ijms24108873.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaCS patientsEarly recurrenceDroplet digital polymerase chain reactionCA 125Serous carcinomaCtDNA testingTime of surgeryTime of recurrenceReliable tumor biomarkersTumour DNA biomarkersCarcinosarcoma patientsUSC patientsRecurrent diseaseOccult diseaseOverall survivalEndometrial cancerAggressive variantInitial treatmentRecurrent tumorsResidual tumorClinical findingsTreatment courseTreatment trialsPIK3CA mutations
2020
Randomized phase II trial of carboplatin-paclitaxel compared to carboplatin-paclitaxel-trastuzumab in advanced or recurrent uterine serous carcinomas that overexpress HER2/Neu (NCT01367002): Updated survival analysis
Fader A, Roque D, Siegel E, Buza N, Hui P, Havrilesky L, Secord A, O'Malley D, Backes F, Nevadunsky N, Chambers S, Edraki B, Celano P, Bellone S, Azodi M, Ratner E, Litkouhi B, Silasi D, Schwartz P, Santin A. Randomized phase II trial of carboplatin-paclitaxel compared to carboplatin-paclitaxel-trastuzumab in advanced or recurrent uterine serous carcinomas that overexpress HER2/Neu (NCT01367002): Updated survival analysis. Gynecologic Oncology 2020, 159: 7-8. DOI: 10.1016/j.ygyno.2020.06.014.Peer-Reviewed Original Research
2015
PIK3CA oncogenic mutations represent a major mechanism of resistance to trastuzumab in HER2/neu overexpressing uterine serous carcinomas
Black J, Lopez S, Cocco E, Bellone S, Altwerger G, Schwab C, English D, Bonazzoli E, Predolini F, Ferrari F, Ratner E, Silasi D, Azodi M, Schwartz P, Santin A. PIK3CA oncogenic mutations represent a major mechanism of resistance to trastuzumab in HER2/neu overexpressing uterine serous carcinomas. Gynecologic Oncology 2015, 139: 596. DOI: 10.1016/j.ygyno.2015.09.058.Peer-Reviewed Original ResearchMutations in the PIK3 pathway as a major determinant of trastuzumab resistance in uterine serous carcinoma
Black J, Lopez S, Bellone S, Schwab C, English D, Roque D, Silasi D, Ratner E, Azodi M, Rutherford T, Schwartz P, Santin A. Mutations in the PIK3 pathway as a major determinant of trastuzumab resistance in uterine serous carcinoma. Gynecologic Oncology 2015, 137: 161-162. DOI: 10.1016/j.ygyno.2015.01.404.Peer-Reviewed Original Research