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 immunohistochemistryEfficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients
Ortigoza MB, Yoon H, Goldfeld KS, Troxel AB, Daily JP, Wu Y, Li Y, Wu D, Cobb GF, Baptiste G, O’Keeffe M, Corpuz MO, Ostrosky-Zeichner L, Amin A, Zacharioudakis IM, Jayaweera DT, Wu Y, Philley JV, Devine MS, Desruisseaux MS, Santin AD, Anjan S, Mathew R, Patel B, Nigo M, Upadhyay R, Kupferman T, Dentino AN, Nanchal R, Merlo CA, Hager DN, Chandran K, Lai JR, Rivera J, Bikash CR, Lasso G, Hilbert TP, Paroder M, Asencio AA, Liu M, Petkova E, Bragat A, Shaker R, McPherson DD, Sacco RL, Keller MJ, Grudzen CR, Hochman JS, Pirofski LA, Rahman F, Ajayi A, Rodriguez S, Ledesma A, Keeling D, Rappoport N, Ebel S, Kim J, Chang M, Chan K, Patel P, Martocci A, Dave S, Darwish Y, Taveras M, Shoyelu V, Xin P, Iturrate E, Moldolsky L, Raimondo B, Mendez S, Hughes P, Sterling S, Lord A, Yaghi S, Veloso K, Sheikh M, Visconti-Ferrara E, Fleming A, Youn H, Jane Fran B, Medina R, McKell R, Khan S, Hamilton T, Sanchez C, Patel N, Cleare L, Vergnolle O, Nakouzi A, Quevedo G, Bortz R, Wirchnianski A, Florez C, Babb R, Ayala J, Tsagaris K, James A, Eke I, Obeidallah A, Sandu O, Sohval S, Serrano-Rahman L, Uehlinger J, Bartash R, Al-Abduladheem A, Gendlina I, Sheridan C, Bortnick A, Eichler J, Kaufman R, Yukelis S, Pennock M, Goggin M, Shen C, Annam J, Khokhar A, Barboto D, Lally B, Lee A, Lee M, Yang X, Allen S, Malaviya A, Moussa O, Park R, Sample R, Bae A, Benoni G, Boerger L, Baker L, Luther M, Ameti L, Briggs N, Golden M, Gormally M, Huang G, Johnson R, Morrison A, Montagna-Hill M, Rivera B, Cortezzo G, Debski K, Nicoletti, DeBenedictis K, Davis R, Marshall C, Duque Cuartas M, Beauchamps L, Bertran-Lopez J, Gonzales Zamora J, Delgado-Lelievre M, Dominguez S, Lee C, Kusack H, Karakeshishyan V, Hajaz A, Deniz D, Garcia G, Dae K, Blenet P, Jaffe D, Olson L, Sabogal D, Blust O, Del Prete Perez V, Bornia C, Rodriguez-Perez V, Calderon V, Ramdev R, Jolly A, Guzman I, Guerra R, Brito S, Hobbs R, Denham R, Dick J, Hernandez M, Nielsen L, Anjum S, Mader S, Stutz T, Mammadova M, Nichols P, Khan T, Boktour M, Castaneda B, Benitez B, Hinojosa E, Guerra B, Ortiz A, Hebbeler-Clark R, McShane P, Hibbard R, Hawkins B, Dohanich E, Wadle C, Greenlee K, Brooks J, Herrick C, Gode A, Bergl P, Hu K, Patel J, Srinivasan S, Graf J, Klis C, Reimer K, Carpenter E, Naczek C, Petersen R, Dex R, Drossart J, Zelten J, Brummitt C, Liang M, Yanny L, Dennison G, Runningen P, Brzezinski B, Fiebig S, Naczek C, Kasdorf M, Parameswaran L, Corcoran A, Rohatgi A, Wronska M, Wu X, Srinivasan R, Deng F, Filardo T, Pendse J, Blaser S, Whyte O, Gallagher J, Thomas O, Ramos D, Sturm-Reganato C, Fong C, Daus I, Payoen A, Chiofolo J, Friedman M, Wu D, Jacobson J, Schneider J, Sarwar U, Wang H, Huebinger R, Dronavalli G, Bai Y, Grimes C, Eldin K, Umana V, Martin J, Heath T, Bello F, Ransford D, Laurent-Rolle M, Shenoi S, Akide-Ndunge O, Thapa B, Peterson J, Knauf K, Patel S, Cheney L, Tormey C, Hendrickson J. Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients. JAMA Internal Medicine 2022, 182: 115-126. PMID: 34901997, PMCID: PMC8669605, DOI: 10.1001/jamainternmed.2021.6850.Peer-Reviewed Original ResearchConceptsCCP recipientsPlacebo recipientsSecondary outcomesSymptom durationHospitalized patientsPrimary outcomeDay 28COVID-19SARS-CoV-2 serostatusSARS-CoV-2 titersWorld Health Organization (WHO) ordinal scaleCOVID-19 convalescent plasmaConvalescent plasma usePlacebo-controlled trialLess daysExploratory subgroup analysisNon-Hispanic blacksSARS-CoV-2CCP efficacyConcomitant medicationsAdverse eventsClinical improvementSymptom onsetConvalescent plasmaMedian ageLenvatinib 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
O002/#43 Randomized phase 3 study of lenvatinib plus pembrolizumab for advanced endometrial cancer (aec): subgroup analysis of patients with DNA mismatch repair deficient (DMMR) tumors
Makker V, Colombo N, Herráez A, Santin A, Colomba E, Miller D, Fujiwara K, Pignata S, Banerjee S, Monk B, Ushijima K, Penson R, Kristeleit R, Fabbro M, Orlando M, Mackay H, Ren M, Orlowski R, Dutta L, Lorusso D. O002/#43 Randomized phase 3 study of lenvatinib plus pembrolizumab for advanced endometrial cancer (aec): subgroup analysis of patients with DNA mismatch repair deficient (DMMR) tumors. International Journal Of Gynecological Cancer 2021, 31: a1-a2. DOI: 10.1136/ijgc-2021-igcs.2.Peer-Reviewed Original ResearchTPC groupDNA mismatch repair deficient tumorsPrior platinum-based chemotherapy regimenMismatch repair-proficient tumorsPlatinum-based chemotherapy regimenTreatment-emergent adverse eventsRandomized phase 3 studyMismatch repair-deficient tumorsBlinded independent central reviewManageable safety profileAdvanced endometrial cancerPhase 3 studyPlatinum-based therapyIndependent central reviewRepair-deficient tumorsRECIST v1.1Chemotherapy regimenAdverse eventsEndometrial cancerProficient tumorsCentral reviewDMMR patientsSafety profileSubgroup analysisPatientsTrastuzumab tolerability in the treatment of advanced (stage III-IV) or recurrent uterine serous carcinomas that overexpress HER2/neu
Tymon-Rosario J, Siegel ER, Bellone S, Harold J, Adjei N, Zeybek B, Mauricio D, Altwerger G, Menderes G, Ratner E, Clark M, Andikyan V, Huang GS, Azodi M, Schwartz PE, Fader AN, Santin AD. Trastuzumab tolerability in the treatment of advanced (stage III-IV) or recurrent uterine serous carcinomas that overexpress HER2/neu. Gynecologic Oncology 2021, 163: 93-99. PMID: 34372971, PMCID: PMC8721852, DOI: 10.1016/j.ygyno.2021.07.033.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaRecurrent uterine serous carcinomaAdverse eventsTreatment armsSerous carcinomaExperimental armToxicity profileTreatment-related adverse eventsTrastuzumab maintenance therapyCarboplatin/paclitaxelCardiac adverse eventsEndometrial cancer patientsGastrointestinal adverse eventsManageable toxicity profilePhase II trialEfficacy of trastuzumabSystem organ classII trialMaintenance therapyPrimary endpointSecondary endpointsMaintenance treatmentSafety profileCancer patientsCumulative toxicityA phase II evaluation of pembrolizumab in recurrent microsatellite instability-high (MSI-H) endometrial cancer patients with Lynch-like versus MLH-1 methylated characteristics (NCT02899793).
Roque D, Bellone S, Siegel E, Buza N, Bonazzoli E, Guglielmi A, Zammataro L, Nagarkatti N, Zaidi S, Lee J, Schwartz P, Ratner E, Alexandrov L, Iwasaki A, Kong Y, Song E, Dong W, Elvin J, Choi J, Santin A. A phase II evaluation of pembrolizumab in recurrent microsatellite instability-high (MSI-H) endometrial cancer patients with Lynch-like versus MLH-1 methylated characteristics (NCT02899793). Journal Of Clinical Oncology 2021, 39: 5523-5523. DOI: 10.1200/jco.2021.39.15_suppl.5523.Peer-Reviewed Original ResearchObjective response rateImmune checkpoint inhibitorsEndometrial cancer patientsTumor mutational burdenCancer patientsGrade 3/4 treatment-related adverse eventsSolid Tumors version 1.1Treatment-related adverse eventsSporadic tumorsPhase II pilot studyOverall survival proportionPrimary end pointResponse Evaluation CriteriaPhase II evaluationAntigen processing/presentationProcessing/presentationAdverse eventsICI resistancePrognostic significanceMechanisms of resistancePolymerase chain reactionII evaluationClinical studiesMutational burdenPatientsEvaluation of treatment effects in patients with endometrial cancer and POLE mutations: An individual patient data meta‐analysis
McAlpine JN, Chiu DS, Nout RA, Church DN, Schmidt P, Lam S, Leung S, Bellone S, Wong A, Brucker SY, Lee CH, Clarke BA, Huntsman DG, Bernardini MQ, Ngeow J, Santin AD, Goodfellow P, Levine DA, Köbel M, Kommoss S, Bosse T, Gilks CB, Talhouk A. Evaluation of treatment effects in patients with endometrial cancer and POLE mutations: An individual patient data meta‐analysis. Cancer 2021, 127: 2409-2422. PMID: 33793971, DOI: 10.1002/cncr.33516.Peer-Reviewed Original ResearchConceptsIndividual patient dataEndometrial cancerPOLE mutationsAdjuvant treatmentAdverse eventsSalvage rateClinical outcomesMeta-analyses (PRISMA) reporting guidelinesConcerns of overtreatmentPathogenic POLE mutationsPatient dataEvidence of diseaseRecurrence/progressionTraditional prognostic factorsProgression/recurrenceUnfavorable pathological featuresAssociation of treatmentMixed effects Cox modelPreferred Reporting ItemsAdditional therapyAdjuvant therapyLess therapyPrognostic factorsFirst diagnosisPathological featuresQuality of Life and Adverse Events: Prognostic Relationships in Long-Term Ovarian Cancer Survival
Wenzel L, Osann K, McKinney C, Cella D, Fulci G, Scroggins MJ, Lankes HA, Wang V, Nephew KP, Maxwell GL, Mok SC, Conrads TP, Miller A, Mannel RS, Gray HJ, Hanjani P, Huh WK, Spirtos N, Leitao MM, Glaser G, Sharma SK, Santin AD, Sperduto P, Lele SB, Burger RA, Monk BJ, Birrer M. Quality of Life and Adverse Events: Prognostic Relationships in Long-Term Ovarian Cancer Survival. Journal Of The National Cancer Institute 2021, 113: 1369-1378. PMID: 33729494, PMCID: PMC8486331, DOI: 10.1093/jnci/djab034.Peer-Reviewed Original ResearchConceptsLong-term survivorsShort-term survivorsQuality of lifeOvarian cancer survivalLong-term survivalAdverse eventsCancer survivalBaseline QOLCancer Therapy-OvarianTrial Outcome IndexMeaningful prognostic valueLongitudinal mixed modelsAE gradeRobust prognosticatorPatient characteristicsPrognostic valueQoL changesSurvivor groupGOG 218Prognostic relationshipOutcome indexTrial designFunctional assessmentCare implicationsChange scoresSacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial
Bardia A, Messersmith WA, Kio EA, Berlin JD, Vahdat L, Masters GA, Moroose R, Santin AD, Kalinsky K, Picozzi V, O'Shaughnessy J, Gray JE, Komiya T, Lang JM, Chang JC, Starodub A, Goldenberg DM, Sharkey RM, Maliakal P, Hong Q, Wegener WA, Goswami T, Ocean AJ. Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial. Annals Of Oncology 2021, 32: 746-756. PMID: 33741442, DOI: 10.1016/j.annonc.2021.03.005.Peer-Reviewed Original ResearchConceptsOverall safety populationAdverse eventsSacituzumab govitecanAntibody-drug conjugatesEpithelial cancersFebrile neutropeniaMost common treatment-related adverse eventsPhase I/II multicenter trialCommon treatment-related adverse eventsTreatment-related serious adverse eventsTrophoblast cell surface antigen 2Castrate-resistant prostate cancer patientsTreatment-related adverse eventsCastrate-resistant prostate cancerSmall cell lung cancerCell surface antigen 2Clinical benefit rateTreatment-related deathsObjective response rateSerious adverse eventsProgression-free survivalDuration of responseAdvanced epithelial cancersProstate cancer patientsSmall cell lung
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 lines
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
Sacituzumab Govitecan (IMMU-132) in treatment-resistant uterine serous carcinoma: A case report
Han C, Bellone S, Schwartz PE, Govindan SV, Sharkey RM, Goldenberg DM, Santin AD. Sacituzumab Govitecan (IMMU-132) in treatment-resistant uterine serous carcinoma: A case report. Gynecologic Oncology Reports 2018, 25: 37-40. PMID: 29977989, PMCID: PMC6030029, DOI: 10.1016/j.gore.2018.05.009.Peer-Reviewed Original ResearchUterine serous carcinomaSacituzumab govitecanAntibody-drug conjugatesSerous carcinomaTreatment optionsNovel antibody-drug conjugateTreatment-resistant diseaseImpressive clinical responsesSignificant adverse eventsEffective treatment optionNew treatment optionsSerial CT scansUSC patientsAdverse eventsClinical responseMultiple chemotherapyAggressive variantCase reportUterine cancerClinical trialsCT scanDramatic responseSurface antigenTrop-2Chemotherapy
2016
Platinum desensitization in patients with carboplatin hypersensitivity: A single-institution retrospective study
Altwerger G, Gressel GM, English DP, Nelson WK, Carusillo N, Silasi DA, Azodi M, Santin A, Schwartz PE, Ratner ES. Platinum desensitization in patients with carboplatin hypersensitivity: A single-institution retrospective study. Gynecologic Oncology 2016, 144: 77-82. PMID: 27789084, DOI: 10.1016/j.ygyno.2016.09.027.Peer-Reviewed Original ResearchConceptsPositive skin testsHypersensitivity reactionsDesensitization protocolSkin testCarboplatin infusionLife-threatening hypersensitivity reactionSingle-institution retrospective studyCarboplatin desensitization protocolPrior hypersensitivity reactionMajority of patientsCarboplatin hypersensitivity reactionsCarboplatin hypersensitivityPulmonary hypertensionAdverse eventsRetrospective reviewRetrospective studyGynecologic cancerGrade 0Patient deathRisk factorsCardiac conditionsPatientsLarger studyInfusionAge
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