2023
HER2 Oncogene as Molecular Target in Uterine Serous Carcinoma and Uterine Carcinosarcoma
McNamara B, Mutlu L, Greenman M, Harold J, Santin A. HER2 Oncogene as Molecular Target in Uterine Serous Carcinoma and Uterine Carcinosarcoma. Cancers 2023, 15: 4085. PMID: 37627113, PMCID: PMC10452357, DOI: 10.3390/cancers15164085.Peer-Reviewed Original ResearchUterine serous carcinomaHuman epidermal growth factor receptor 2Uterine carcinosarcomaSerous carcinomaTraditional platinum-based chemotherapyEpidermal growth factor receptor 2Growth factor receptor 2Platinum-based chemotherapyOngoing clinical trialsRare histologic variantHER2 protein overexpressionAggressive metastatic potentialFactor receptor 2Distinct molecular profilesPreclinical evidenceUterine carcinomaHistologic variantsClinical trialsHER2 oncogeneReceptor 2Metastatic potentialCarcinomaMolecular profileMolecular targetsProtein overexpressionPreliminary 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 1
2022
Lenvatinib Plus Pembrolizumab for Advanced Endometrial Cancer
Makker V, Colombo N, Herráez A, Santin A, Colomba E, Miller D, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Sakata J, Yonemori K, Kim Y, Guerra E, Sanli U, McCormack M, Smith A, Keefe S, Bird S, Dutta L, Orlowski R, Lorusso D. Lenvatinib Plus Pembrolizumab for Advanced Endometrial Cancer. Obstetrical & Gynecological Survey 2022, 77: 275-276. DOI: 10.1097/ogx.0000000000001032.Peer-Reviewed Original ResearchEndometrial cancerRecurrent endometrial cancerSecond-line treatmentAdvanced endometrial cancerPlatinum-based chemotherapyRecurrent endometrial carcinomaTyrosine kinase inhibitorsEndometrial carcinomaOptimal treatmentDisease progressionLimited efficacySingle agentKinase inhibitorsLenvatinibCancerTreatmentPembrolizumabLittle consensusChemotherapyCarcinomaProgressionLenvatinib plus Pembrolizumab for Advanced Endometrial Cancer
Makker V, Colombo N, Casado Herráez A, Santin AD, Colomba E, Miller DS, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Sakata J, Yonemori K, Kim YM, Guerra EM, Sanli UA, McCormack MM, Smith AD, Keefe S, Bird S, Dutta L, Orlowski RJ, Lorusso D. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer. New England Journal Of Medicine 2022, 386: 437-448. PMID: 35045221, DOI: 10.1056/nejmoa2108330.Peer-Reviewed Original ResearchConceptsAdvanced endometrial cancerProgression-free survivalEndometrial cancerOverall survivalMedian progression-free survivalPlatinum-based chemotherapy regimenLonger progression-free survivalEnd pointBlinded independent central reviewMedian overall survivalPrimary end pointPhase 3 trialResponse Evaluation CriteriaPlatinum-based chemotherapyIndependent central reviewChemotherapy regimenAdverse eventsStandard therapyCentral reviewPembrolizumabGrade 3LenvatinibChemotherapyPhysician's choicePatients
2021
O008/#785 A multicenter, open-label, randomized, phase 3 study to compare the efficacy and safety of lenvatinib in combination with pembrolizumab vs treatment of physician’s choice in patients with advanced endometrial cancer: study 309/keynote-775
Makker V, Colombo N, Herráez A, Santin A, Colomba E, Miller D, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira R, Ushijima K, Sakata J, Yonemori K, Kim Y, Guerra E, Sanli U, Mccormack M, Huang J, Smith A. O008/#785 A multicenter, open-label, randomized, phase 3 study to compare the efficacy and safety of lenvatinib in combination with pembrolizumab vs treatment of physician’s choice in patients with advanced endometrial cancer: study 309/keynote-775. International Journal Of Gynecological Cancer 2021, 31: a4-a5. DOI: 10.1136/ijgc-2021-igcs.8.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsAdvanced endometrial cancerObjective response rateEndometrial cancerPhysician's choiceCommon treatment-emergent adverse eventsPrior platinum-based chemotherapy regimenPhase 3 study resultsPlatinum-based chemotherapy regimenPrior platinum-based chemotherapyDNA mismatch repair (MMR) statusBlinded independent central reviewPhase 1b/2 studySafety of lenvatinibKey secondary endpointMedian treatment durationAdvanced endometrial carcinomaPhase 3 studyPlatinum-based chemotherapyIndependent central reviewPlatinum-based therapyMismatch repair statusEligible ptsRECIST v1.1Adjuvant settingA multicenter, open-label, randomized, phase III study to compare the efficacy and safety of lenvatinib in combination with pembrolizumab versus treatment of physician's choice in patients with advanced endometrial cancer
Makker V, Colombo N, Herráez A, Santin A, Colomba E, Miller D, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Sakata J, Yonemori K, Kim Y, Guerra E, Sanli U, McCormack M, Huang J, Smith A, Keefe S, Dutta L, Orlowski R, Lorusso D. A multicenter, open-label, randomized, phase III study to compare the efficacy and safety of lenvatinib in combination with pembrolizumab versus treatment of physician's choice in patients with advanced endometrial cancer. Gynecologic Oncology 2021, 162: s4. DOI: 10.1016/s0090-8258(21)00657-0.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsAdvanced endometrial cancerObjective response rateEndometrial cancerPhysician's choiceCommon treatment-emergent adverse eventsGrade treatment-emergent adverse eventsPrior platinum-based chemotherapy regimenPhase III study resultsPlatinum-based chemotherapy regimenPrior platinum-based chemotherapyDNA mismatch repair (MMR) statusBlinded independent central reviewPhase 1b/2 studySafety of lenvatinibKey secondary endpointMedian treatment durationAdvanced endometrial carcinomaPlatinum-based chemotherapyIndependent central reviewPlatinum-based therapyMismatch repair statusAdjuvant settingChemotherapy regimenECOG PS
2020
TROPiCS–03: A phase II open-label study of sacituzumab govitecan (SG) in patients with metastatic solid tumors.
Saxena A, Michel L, Hong Q, Hilsinger K, Kanwal C, Pichardo C, Goswami T, Santin A. TROPiCS–03: A phase II open-label study of sacituzumab govitecan (SG) in patients with metastatic solid tumors. Journal Of Clinical Oncology 2020, 38: tps3648-tps3648. DOI: 10.1200/jco.2020.38.15_suppl.tps3648.Peer-Reviewed Original ResearchMetastatic solid tumorsSacituzumab govitecanTrop-2 expressionSolid tumorsPhase II open-label studyPrior platinum-based chemotherapyCell death protein 1Neck squamous cell carcinomaActive CNS metastasesClinical benefit rateOverall safety populationManageable safety profileObjective response rateOpen-label studyLow discontinuation ratePhase 2 studyProgression-free survivalPlatinum-based chemotherapyDeath protein 1Duration of responseSquamous cell carcinomaCell surface antigensBiomarker enrichment strategiesMultiple tumor typesTopoisomerase I inhibitorPhase II evaluation of nivolumab in the treatment of persistent or recurrent cervical cancer (NCT02257528/NRG-GY002)
Santin AD, Deng W, Frumovitz M, Buza N, Bellone S, Huh W, Khleif S, Lankes HA, Ratner ES, O'Cearbhaill RE, Jazaeri AA, Birrer M. Phase II evaluation of nivolumab in the treatment of persistent or recurrent cervical cancer (NCT02257528/NRG-GY002). Gynecologic Oncology 2020, 157: 161-166. PMID: 31924334, PMCID: PMC7127981, DOI: 10.1016/j.ygyno.2019.12.034.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsRecurrent cervical cancerPD-L1 expressionPlatinum-based chemotherapyCervical cancerStable diseaseGrade 3 treatment-related adverse eventsGrade 4 treatment-related adverse eventsGrade 5 treatment-related adverse eventsECOG PS 0Prior systemic therapyRecurrent cervical carcinomaResponse/toxicitySingle-agent nivolumabSystemic chemotherapy regimenTolerability of nivolumabImmune checkpoint inhibitorsPercent of patientsAcceptable safety profilePhase II trialKey eligibility criteriaPhase II evaluationECOG PSNivolumab 3RECIST 1.1
2019
Synergistic clinical efficacy of niraparib in combination with pembrolizumab in patients with recurrent platinum-resistant ovarian carcinoma
Tymon-Rosario J, Zeybek B, Han C, Santin AD. Synergistic clinical efficacy of niraparib in combination with pembrolizumab in patients with recurrent platinum-resistant ovarian carcinoma. Annals Of Translational Medicine 2019, 0: s308. PMID: 32016027, PMCID: PMC6976388, DOI: 10.21037/atm.2019.10.28.Peer-Reviewed Original ResearchPlatinum-based chemotherapyOvarian cancerInitial platinum-based chemotherapyPlatinum-resistant ovarian carcinomaGynecologic cancer deathStandard treatment regimenCancer respondMost patientsTreatment regimenClinical efficacyCancer deathOvarian carcinomaCommon causeDeath rateCancerPrecision medicineChemotherapyPatientsToxic effectsDeathPembrolizumabRegimenCarcinomaTherapyNiraparib
2016
Polymerase ε (POLE) ultra-mutation in uterine tumors correlates with T lymphocyte infiltration and increased resistance to platinum-based chemotherapy in vitro
Bellone S, Bignotti E, Lonardi S, Ferrari F, Centritto F, Masserdotti A, Pettinella F, Black J, Menderes G, Altwerger G, Hui P, Lopez S, de Haydu C, Bonazzoli E, Predolini F, Zammataro L, Cocco E, Ferrari F, Ravaggi A, Romani C, Facchetti F, Sartori E, Odicino FE, Silasi DA, Litkouhi B, Ratner E, Azodi M, Schwartz PE, Santin AD. Polymerase ε (POLE) ultra-mutation in uterine tumors correlates with T lymphocyte infiltration and increased resistance to platinum-based chemotherapy in vitro. Gynecologic Oncology 2016, 144: 146-152. PMID: 27894751, PMCID: PMC5183545, DOI: 10.1016/j.ygyno.2016.11.023.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsCarboplatinCarcinomaCD4 Lymphocyte CountCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell SurvivalDisease-Free SurvivalDNA Polymerase IIDrug Resistance, NeoplasmEndometrial NeoplasmsFemaleHumansMicrosatellite InstabilityMiddle AgedMutationPoly-ADP-Ribose Binding ProteinsTumor Cells, CulturedConceptsBetter prognosisTumor cell linesInfiltration of CD4Number of CD4Platinum-based chemotherapyT lymphocyte infiltrationPD-1 receptorCell linesLow metastatic capabilityPOLE-mutated tumorsWild-type ECsEC cell linesLymphocyte infiltrationFavorable prognosisPD-1EC patientsType tumorsEnhanced immunogenicityT lymphocytesMolecular subtypesTumors correlatesChemotherapyMetastatic capabilityPrognosisTumors
2012
Prognostic factors and treatment-related outcomes in patients with uterine serous cancer (USC).
deLeon M, Lu L, Hui P, Santin A, Rutherford T, Arin-Silasi D, Azodi M, Ratner E, Schwartz P. Prognostic factors and treatment-related outcomes in patients with uterine serous cancer (USC). Journal Of Clinical Oncology 2012, 30: 5099-5099. DOI: 10.1200/jco.2012.30.15_suppl.5099.Peer-Reviewed Original ResearchStage IA/IBDisease-free survivalUterine serous cancerIIIA/IIIBIVA/IVBIA/IBUSC patientsPrognostic factorsMyometrial invasionLargest single-institution experienceWhole-pelvis radiation therapyLymph node involvementPlatinum-based chemotherapySingle institution experienceIndependent prognostic factorLymph node metastasisTreatment-related outcomesUterine cancer deathsBetter OSII-IVBIB diseaseNode involvementSurgical debulkingSerous cancerShorter OS
2010
Differential sensitivity to platinum-based chemotherapy in primary uterine serous papillary carcinoma cell lines with high vs low HER-2/neu expression in vitro
Cross SN, Cocco E, Bellone S, Anagnostou VK, Brower SL, Richter CE, Siegel ER, Schwartz PE, Rutherford TJ, Santin AD. Differential sensitivity to platinum-based chemotherapy in primary uterine serous papillary carcinoma cell lines with high vs low HER-2/neu expression in vitro. American Journal Of Obstetrics And Gynecology 2010, 203: 162.e1-162.e8. PMID: 20417484, PMCID: PMC2918912, DOI: 10.1016/j.ajog.2010.02.056.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsApoptosisCarboplatinCell Line, TumorCell ProliferationCisplatinCystadenocarcinoma, PapillaryCystadenocarcinoma, SerousDrug Resistance, NeoplasmFemaleGene Expression Regulation, NeoplasticHumansMiddle AgedProbabilityReceptor, ErbB-2Sensitivity and SpecificityUterine NeoplasmsConceptsSingle-agent chemotherapyLow HER-2/neu expressionCell linesHER-2/neu expressionEffective chemotherapy regimensPlatinum-based chemotherapySerous papillary adenocarcinomaHalf-maximum inhibitory concentrationPlatinum compoundsLow half-maximum inhibitory concentrationChemotherapy regimensAdverse prognosisPapillary adenocarcinomaCarcinoma cell linesNeu expressionNeu overexpressionChemotherapy agentsPapillary carcinoma cell line