2024
Efficacy and Safety of Sacituzumab Govitecan in Patients With Advanced Solid Tumors (TROPiCS-03): Analysis in Patients With Advanced Endometrial Cancer
Santin A, Corr B, Spira A, Willmott L, Butrynski J, Tse K, Patel J, Mekan S, Wu T, Lin K, Kuo P, Dumbrava E. Efficacy and Safety of Sacituzumab Govitecan in Patients With Advanced Solid Tumors (TROPiCS-03): Analysis in Patients With Advanced Endometrial Cancer. Journal Of Clinical Oncology 2024, 42: 3421-3429. PMID: 39083724, PMCID: PMC11458108, DOI: 10.1200/jco.23.02767.Peer-Reviewed Original ResearchProgression-free survivalDuration of responseTreatment-related adverse eventsAdvanced endometrial cancerEndometrial cancerSacituzumab govitecanTrop-2Investigator assessmentSolid tumorsTrophoblast cell surface antigen 2Median duration of responsePhase II basket studyMedian progression-free survivalEnd pointsBaseline tumor specimensClinical benefit ratePlatinum-based therapyStudy drug discontinuationAdvanced solid tumorsMedian follow-upMetastatic solid tumorsTrop-2 expressionSecondary end pointsPrimary end pointEfficacy of SG
2023
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).
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 PS
2022
Safety and activity of anti-mesothelin antibody–drug conjugate anetumab ravtansine in combination with pegylated-liposomal doxorubicin in platinum-resistant ovarian cancer: multicenter, phase Ib dose escalation and expansion study
Santin A, Vergote I, González-Martín A, Moore K, Oaknin A, Romero I, Diab S, Copeland L, Monk B, Coleman R, Herzog T, Siegel J, Kasten L, Schlicker A, Schulz A, Köchert K, Walter A, Childs B, Elbi C, Bulat I. Safety and activity of anti-mesothelin antibody–drug conjugate anetumab ravtansine in combination with pegylated-liposomal doxorubicin in platinum-resistant ovarian cancer: multicenter, phase Ib dose escalation and expansion study. International Journal Of Gynecological Cancer 2022, 33: ijgc-2022-003927. PMID: 36564099, PMCID: PMC10086500, DOI: 10.1136/ijgc-2022-003927.Peer-Reviewed Original ResearchConceptsPlatinum-resistant ovarian cancerProgression-free survivalMedian progression-free survivalAnetumab ravtansineObjective response rateOvarian cancerLiposomal doxorubicinMedian durationAdverse eventsDose escalationMesothelin expressionCommon treatment-emergent adverse eventsPlatinum-resistant epithelial ovarian cancerResponse rateAnti-mesothelin monoclonal antibodyTreatment-emergent adverse eventsHigh mesothelin expressionPegylated-liposomal doxorubicinPhase Ib studyPhase III studyDose-limiting toxicityPromising clinical activityEpithelial ovarian cancerAnti-tumor activityCentral immunohistochemistryLenvatinib 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 choicePatientsRandomized Phase III Trial of Paclitaxel and Carboplatin Versus Paclitaxel and Ifosfamide in Patients With Carcinosarcoma of the Uterus or Ovary: An NRG Oncology Trial
Powell MA, Filiaci VL, Hensley ML, Huang HQ, Moore KN, Tewari KS, Copeland LJ, Secord AA, Mutch DG, Santin A, Warshal DP, Spirtos NM, DiSilvestro PA, Ioffe OB, Miller DS. Randomized Phase III Trial of Paclitaxel and Carboplatin Versus Paclitaxel and Ifosfamide in Patients With Carcinosarcoma of the Uterus or Ovary: An NRG Oncology Trial. Journal Of Clinical Oncology 2022, 40: 968-977. PMID: 35007153, PMCID: PMC8937015, DOI: 10.1200/jco.21.02050.Peer-Reviewed Original ResearchConceptsProgression-free survivalUterine carcinosarcomaOvarian carcinosarcomaEligible patientsHazard ratioMore patientsPC armMedian progression-free survivalRandomized phase III trialNRG Oncology trialsPhase III trialsPI armsGenitourinary hemorrhageHematologic toxicityMedian OSIII trialsLonger OSStandard treatmentGreater death rateStage IIINoninferiority designOncology trialsPatientsStage IStage IV
2020
372 Safety and activity of the anti-mesothelin antibody–drug conjugate anetumab ravtansine in combination with pegylated-liposomal doxorubicin in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer
Santin A, Vergote I, Martín A, Moore K, Oaknin A, Romero I, Diab S, Copeland L, Monk B, Coleman R, Herzog T, Siegel J, Walter A, Childs B, Elbi C, Bulat I. 372 Safety and activity of the anti-mesothelin antibody–drug conjugate anetumab ravtansine in combination with pegylated-liposomal doxorubicin in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer. International Journal Of Gynecological Cancer 2020, 30: a154-a154. DOI: 10.1136/ijgc-2020-igcs.322.Peer-Reviewed Original ResearchPlatinum-resistant ovarian cancerProgression-free survivalObjective response rateMedian progression-free survivalPLD combinationAdverse eventsMesothelin expressionClinical activityAnti-mesothelin monoclonal antibodyHigh mesothelin expressionObserved clinical activityPegylated-liposomal doxorubicinSafety/tolerabilityPrimary peritoneal cancerPhase III studyHigh medical needAnetumab ravtansineCentral immunohistochemistryEvaluable patientsExploratory subsetPeritoneal cancerIII studyMedian durationPartial responsePrior linesNeratinib in patients with HER2-mutant, metastatic cervical cancer: Findings from the phase 2 SUMMIT basket trial
Oaknin A, Friedman CF, Roman LD, D’Souza A, Brana I, Bidard F, Goldman J, Alvarez EA, Boni V, ElNaggar AC, Passalacqua R, T.M. K, Santin AD, Keyvanjah K, Xu F, Eli LD, Lalani AS, Bryce RP, Hyman DM, Meric-Bernstam F, Solit DB, Monk BJ. Neratinib in patients with HER2-mutant, metastatic cervical cancer: Findings from the phase 2 SUMMIT basket trial. Gynecologic Oncology 2020, 159: 150-156. PMID: 32723675, PMCID: PMC8336424, DOI: 10.1016/j.ygyno.2020.07.025.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultDiarrheaFemaleHumansKaplan-Meier EstimateMiddle AgedMutationNauseaNeoplasm Recurrence, LocalProgression-Free SurvivalProtein Kinase InhibitorsQuinolinesReceptor, ErbB-2Response Evaluation Criteria in Solid TumorsSeverity of Illness IndexUterine Cervical NeoplasmsConceptsProgression-free survivalClinical benefit rateObjective response rateCervical cancerOverall survivalHER2 mutationsBasket trialsMetastatic/recurrent cervical cancerAdvanced/recurrent diseaseMedian progression-free survivalCommon HER2 mutationsGrade 3 diarrheaGrade 4 eventsHER2-mutant cancersSafety of neratinibCommon adverse eventsMedian overall survivalRecurrent cervical cancerMetastatic cervical cancerNew safety signalsPhase II basket trialPlatinum-based treatmentTyrosine kinase inhibitorsWarrants further investigationEligible patientsSacituzumab govitecan (SG) in patients (pts) with previously treated metastatic endometrial cancer (mEC): results from a phase I/II study.
Santin A, Komiya T, Goldenberg D, Sharkey R, Hong Q, Wegener W, Goswami T, Bardia A. Sacituzumab govitecan (SG) in patients (pts) with previously treated metastatic endometrial cancer (mEC): results from a phase I/II study. Journal Of Clinical Oncology 2020, 38: 6081-6081. DOI: 10.1200/jco.2020.38.15_suppl.6081.Peer-Reviewed Original ResearchMetastatic endometrial cancerObjective response rateClinical benefit rateProgression-free survivalDuration of responseMedian overall survivalSacituzumab govitecanOverall survivalTrop-2 expressionPlatinum therapyPhase I/II studySolid tumorsTrop-2Median progression-free survivalNeutrophil count decreasePrevious preclinical findingsPrior platinum therapySimilar safety profileAdvanced solid tumorsCT/MRI scansMetastatic solid tumorsLimited treatment optionsFurther clinical investigationFebrile neutropeniaPrior chemotherapyPhase II evaluation of copanlisib, a selective inhibitor of Pi3kca, in patients with persistent or recurrent endometrial carcinoma harboring PIK3CA hotspot mutations: An NRG Oncology study (NRG-GY008)
Santin AD, Filiaci V, Bellone S, Ratner ES, Mathews CA, Cantuaria G, Gunderson CC, Rutledge T, Buttin BM, Lankes HA, Frumovitz M, Khleif SN, Huh WK, Birrer MJ. Phase II evaluation of copanlisib, a selective inhibitor of Pi3kca, in patients with persistent or recurrent endometrial carcinoma harboring PIK3CA hotspot mutations: An NRG Oncology study (NRG-GY008). Gynecologic Oncology Reports 2020, 31: 100532. PMID: 31934607, PMCID: PMC6951478, DOI: 10.1016/j.gore.2019.100532.Peer-Reviewed Original ResearchProgression-free survivalStable diseaseOverall survivalMixed histologyPIK3CA mutationsGrade 5 adverse eventsMedian progression-free survivalCommon grade 3Common PIK3CA mutationCTCAE version 4GOG performance statusNRG Oncology StudyMedian overall survivalObjective tumor responsePhase II trialPhase II evaluationBest overall responsePIK3CA gene mutationsPIK3CA hotspot mutationsSelective inhibitorEligible patientsMeasurable diseaseHotspot PIK3CA mutationsII trialPrimary endpoint
2019
Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer
Bardia A, Mayer IA, Vahdat LT, Tolaney SM, Isakoff SJ, Diamond JR, O'Shaughnessy J, Moroose RL, Santin AD, Abramson VG, Shah NC, Rugo HS, Goldenberg DM, Sweidan AM, Iannone R, Washkowitz S, Sharkey RM, Wegener WA, Kalinsky K. Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. New England Journal Of Medicine 2019, 380: 741-751. PMID: 30786188, DOI: 10.1056/nejmoa1814213.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnemiaAntibodies, Monoclonal, HumanizedAntigens, NeoplasmAntineoplastic AgentsCamptothecinCell Adhesion MoleculesDiarrheaDose-Response Relationship, DrugFemaleHumansImmunoconjugatesInfusions, IntravenousIrinotecanMaleMiddle AgedNeutropeniaProgression-Free SurvivalSurvival RateTriple Negative Breast NeoplasmsConceptsMetastatic triple-negative breast cancerTriple-negative breast cancerSacituzumab govitecan-hziyProgression-free survivalClinical benefit rateIndependent central reviewBreast cancerResponse rateAdverse eventsOverall survivalCentral reviewBenefit rateHuman trophoblast cell surface antigen 2Refractory metastatic triple-negative breast cancerTrophoblast cell surface antigen 2Median progression-free survivalSN-38Shorter progression-free survivalCell surface antigen 2Blinded independent central reviewDurable objective responsesPrevious anticancer therapyUnacceptable toxic effectsObjective response rateMain adverse reactions
2018
Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu.
Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, Chambers SK, Secord AA, Havrilesky L, O'Malley DM, Backes F, Nevadunsky N, Edraki B, Pikaart D, Lowery W, ElSahwi KS, Celano P, Bellone S, Azodi M, Litkouhi B, Ratner E, Silasi DA, Schwartz PE, Santin AD. Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu. Journal Of Clinical Oncology 2018, 36: 2044-2051. PMID: 29584549, DOI: 10.1200/jco.2017.76.5966.Peer-Reviewed Original ResearchConceptsHuman epidermal growth factor receptor 2Progression-free survivalUterine serous carcinomaRecurrent uterine serous carcinomaMedian progression-free survivalRandomized phase II trialEpidermal growth factor receptor 2Phase II trialGrowth factor receptor 2Serous carcinomaHER2/neuFactor receptor 2II trialTreatment armsReceptor 2Stage IIIHER2/neu-positive diseaseOne-sided log-rank testMethods Eligible patientsPrimary end pointPrimary stage IIIUnexpected safety signalsLog-rank testHumanized monoclonal antibodyEligible patients
2011
Phase II trial of cetuximab in the treatment of persistent or recurrent squamous or non-squamous cell carcinoma of the cervix: A Gynecologic Oncology Group study
Santin AD, Sill MW, McMeekin DS, Leitao MM, Brown J, Sutton GP, Van Le L, Griffin P, Boardman CH. Phase II trial of cetuximab in the treatment of persistent or recurrent squamous or non-squamous cell carcinoma of the cervix: A Gynecologic Oncology Group study. Gynecologic Oncology 2011, 122: 495-500. PMID: 21684583, PMCID: PMC3152667, DOI: 10.1016/j.ygyno.2011.05.040.Peer-Reviewed Original ResearchConceptsProgression-free survivalGynecologic Oncology GroupPhase II trialSquamous cell histologyII trialCell histologyCell carcinomaGrade 3 adverse eventsMedian progression-free survivalGynecologic Oncology Group studyNon-squamous cell carcinomaGOG performance statusOverall survival timeSquamous cell carcinomaEGFR antibody cetuximabEligible patientsMeasurable diseasePrimary endpointPrior radiationProhibitive toxicityAdverse eventsClinical responseOncology GroupPerformance statusRecurrent carcinoma