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, jco2302767. PMID: 39083724, 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
Lenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775
Makker V, Colombo N, Herráez A, Monk B, Mackay H, Santin A, Miller D, Moore R, Baron-Hay S, Ray-Coquard I, Ushijima K, Yonemori K, Kim Y, Alia E, Sanli U, Bird S, Orlowski R, McKenzie J, Okpara C, Barresi G, Lorusso D. Lenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775. Journal Of Clinical Oncology 2023, 41: 2904-2910. PMID: 37058687, PMCID: PMC10414727, DOI: 10.1200/jco.22.02152.Peer-Reviewed Original ResearchConceptsObjective response rateProgression-free survivalPrimary end pointAdvanced endometrial cancerOverall survivalEndometrial cancerEnd pointMismatch repair-proficient tumorsClinical trial updateMetastatic endometrial cancerNew safety signalsSubgroups of interestManageable safetyPrespecified analysisTrial updateProficient tumorsClinical trialsSafety signalsPembrolizumabLenvatinibPhysician's choiceMultiple end pointsResponse rateSecondary analysisChemotherapyHealth-Related Quality of Life in Patients With Advanced Endometrial Cancer Treated With Lenvatinib Plus Pembrolizumab or Treatment of Physician’s Choice
Lorusso D, Colombo N, Herraez A, Santin A, Colomba E, Miller D, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Kim Y, McCormack M, Massaad R, Nguyen A, Zhao Q, McKenzie J, Prabhu V, Makker V. Health-Related Quality of Life in Patients With Advanced Endometrial Cancer Treated With Lenvatinib Plus Pembrolizumab or Treatment of Physician’s Choice. European Journal Of Cancer 2023, 186: 172-184. PMID: 37086595, PMCID: PMC11003310, DOI: 10.1016/j.ejca.2023.03.015.Peer-Reviewed Original ResearchConceptsAdvanced endometrial cancerEndometrial cancerWeek 12Life QuestionnaireDefinitive deteriorationFunctional scalesPhysician's choiceGlobal health status/qualityFavorable benefit/risk profileHealth status/qualityBenefit/risk profileEuroQol-5 DimensionsHealth-related qualityTreatment of patientsTingling/numbnessImpact of treatmentQuality of lifeRate of completionHRQOL endpointsAppetite lossPoor body imageCancer QualityLife scoresMuscular painSafety resultsMismatch repair deficiency, next-generation sequencing-based microsatellite instability, and tumor mutational burden as predictive biomarkers for immune checkpoint inhibitor effectiveness in frontline treatment of advanced stage endometrial cancer
Hill B, Graf R, Shah K, Danziger N, Lin D, Quintanilha J, Li G, Haberberger J, Ross J, Santin A, Slomovitz B, Elvin J, Eskander R. Mismatch repair deficiency, next-generation sequencing-based microsatellite instability, and tumor mutational burden as predictive biomarkers for immune checkpoint inhibitor effectiveness in frontline treatment of advanced stage endometrial cancer. International Journal Of Gynecological Cancer 2023, 33: 504-513. PMID: 36750267, PMCID: PMC10086481, DOI: 10.1136/ijgc-2022-004026.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsAdvanced endometrial cancerTumor mutational burdenAdjusted hazard ratioEndometrial cancerCheckpoint inhibitorsOverall survivalMismatch repair deficiencyFrontline treatmentMicrosatellite instabilityMutational burdenNext treatmentTreatment discontinuationSingle-agent immune checkpoint inhibitorsAdvanced stage endometrial cancerImmune checkpoint inhibitor effectivenessImmune checkpoint inhibitor monotherapyImmune checkpoint inhibitor treatmentCox proportional hazards modelCheckpoint inhibitor monotherapyStage endometrial cancerPhase III trialsRepair deficiencyCheckpoint inhibitor treatmentLog-rank test
2022
O018/#482 Updated safety of lenvatinib + pembrolizumab vs treatment of physician’s choice in patients with advanced endometrial cancer: study 309/keynote-775
Makker V, Colombo N, Herráez A, Monk B, Mackay H, Santin A, Miller D, Moore R, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Yonemori K, Kim Y, Alia E, Sanli U, Xie R, Zale M, Mckenzie J, Barresi G, Lorusso D. O018/#482 Updated safety of lenvatinib + pembrolizumab vs treatment of physician’s choice in patients with advanced endometrial cancer: study 309/keynote-775. 2022, a11-a11. DOI: 10.1136/ijgc-2022-igcs.20.Peer-Reviewed Original ResearchSafety of lenvatinibAdvanced endometrial cancerEndometrial cancerPhysician's choicePembrolizumabLenvatinibPatientsCancer2022-RA-653-ESGO The impact of histology, prior therapy, and dMMR status on lenvatinib + pembrolizumab outcomes in patients with advanced endometrial cancer: A subgroup analysis of Study 309/KEYNOTE-775
Lorusso D, Makker V, Herraez A, Monk B, Mackay H, Santin A, Miller D, Moore R, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Yonemori K, Kim Y, Guerra Alia E, Sanli U, Huang J, McKenzie J, Barresi G, Colombo N. 2022-RA-653-ESGO The impact of histology, prior therapy, and dMMR status on lenvatinib + pembrolizumab outcomes in patients with advanced endometrial cancer: A subgroup analysis of Study 309/KEYNOTE-775. 2022, a102.1-a102. DOI: 10.1136/ijgc-2022-esgo.223.Peer-Reviewed Original Research525MO Updated efficacy and safety of lenvatinib (LEN) + pembrolizumab (pembro) vs treatment of physician’s choice (TPC) in patients (pts) with advanced endometrial cancer (aEC): Study 309/KEYNOTE-775
Makker V, Colombo N, Herraez A, Monk B, Mackay H, Santin A, Miller D, Moore R, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Yonemori K, Kim Y, Alia E, Sanli U, Huang J, McKenzie J, Barresi G, Lorusso D. 525MO Updated efficacy and safety of lenvatinib (LEN) + pembrolizumab (pembro) vs treatment of physician’s choice (TPC) in patients (pts) with advanced endometrial cancer (aEC): Study 309/KEYNOTE-775. Annals Of Oncology 2022, 33: s785-s786. DOI: 10.1016/j.annonc.2022.07.653.Peer-Reviewed Original ResearchAdvanced endometrial cancerSafety of lenvatinibEndometrial cancerPhysician's choiceLenvatinibPembrolizumabPatientsCancerEfficacy of next line of therapy after treatment with lenvatinib (LEN) in combination with pembrolizumab (pembro) versus treatment of physician’s choice (TPC) in patients (pts) with advanced endometrial cancer (aEC): Exploratory analysis of Study 309/KEYNOTE-775.
Makker V, Colombo N, Santin A, Miller D, Fujiwara K, Pignata S, Ray-Coquard I, Kim Y, Guerra E, Huang J, Barresi G, McKenzie J, Lorusso D. Efficacy of next line of therapy after treatment with lenvatinib (LEN) in combination with pembrolizumab (pembro) versus treatment of physician’s choice (TPC) in patients (pts) with advanced endometrial cancer (aEC): Exploratory analysis of Study 309/KEYNOTE-775. Journal Of Clinical Oncology 2022, 40: 5587-5587. DOI: 10.1200/jco.2022.40.16_suppl.5587.Peer-Reviewed Original ResearchAdvanced endometrial cancerComers populationTPC armEastern Cooperative Oncology Group performance statusPrior platinum-based chemotherapy regimenPlatinum-based chemotherapy regimenObjective response rateOverall survival benefitPrespecified exploratory analysisSystemic anticancer therapyPlatinum-based treatmentMedian PFS2PMMR tumorsChemotherapy regimenPelvic radiationData cutoffPerformance statusEndometrial cancerInvestigator assessmentSurvival benefitStudy treatmentMMR statusLenvatinibPembroPhysician's choice20MO Time to deterioration in quality of life in patients (pts) with advanced endometrial cancer (aEC) treated with lenvatinib plus pembrolizumab (L+P) or treatment of physician’s choice (TPC)
Lorusso D, Colombo N, Herraez A, Santin A, Colomba E, Miller D, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Kim Y, McCormack M, Massaad R, Nguyen A, Zhao Q, McKenzie J, Prabhu V, Makker V. 20MO Time to deterioration in quality of life in patients (pts) with advanced endometrial cancer (aEC) treated with lenvatinib plus pembrolizumab (L+P) or treatment of physician’s choice (TPC). Annals Of Oncology 2022, 33: s391-s392. DOI: 10.1016/j.annonc.2022.04.038.Peer-Reviewed Original ResearchAdvanced endometrial cancerQuality of lifeEndometrial cancerPhysician's choicePembrolizumabLenvatinibPatientsCancerLenvatinib 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
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 analysisPatientsO008/#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 setting145 Characterization of adverse reactions in patients with advanced endometrial cancer (aec) receiving lenvatinib + pembrolizumab (Study 309/KEYNOTE-775)
Colombo N, Lorusso D, Santin A, Kim Y, Herráez A, Yonemori K, Fujiwara K, Colomba E, Miller D, Pignata S, Monk B, Guerra E, Kristeleit R, Orlando M, Sanli U, Dutta L, Orlowski R, Ren M, Makker V. 145 Characterization of adverse reactions in patients with advanced endometrial cancer (aec) receiving lenvatinib + pembrolizumab (Study 309/KEYNOTE-775). International Journal Of Gynecological Cancer 2021, 31: a78-a78. DOI: 10.1136/ijgc-2021-esgo.120.Peer-Reviewed Original ResearchPalmar-plantar erythrodysesthesiaLenvatinib dose reductionAdverse reactionsMusculoskeletal painDose reductionPrior platinum-based therapyAEC patientsTarget lesion diametersCommon adverse reactionsAdvanced endometrial cancerManagement of patientsPlatinum-based therapyQd poEndometrial cancerTreatment initiationMedian timeEndometrial carcinomaHypertensionLenvatinibPrompt identificationPhysician's choiceDiarrheaPatientsFirst onsetMeaningful improvements726MO Outcomes by histology and prior therapy with lenvatinib plus pembrolizumab vs treatment of physician’s choice in patients with advanced endometrial cancer (Study 309/KEYNOTE-775)
Colombo N, Lorusso D, Herráez A, Santin A, Colomba E, Miller D, Fujiwara K, Pignata S, Floquet A, Monk B, Banerjee S, Penson R, Kristeleit R, Fabbro M, Orlando M, Mackay H, Jensen E, Dutta L, Orlowski R, Makker V. 726MO Outcomes by histology and prior therapy with lenvatinib plus pembrolizumab vs treatment of physician’s choice in patients with advanced endometrial cancer (Study 309/KEYNOTE-775). Annals Of Oncology 2021, 32: s729-s730. DOI: 10.1016/j.annonc.2021.08.1169.Peer-Reviewed Original ResearchAdvanced endometrial cancerPrior therapyEndometrial cancerPhysician's choicePembrolizumabLenvatinibPatientsTherapyHistologyCancerA 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
2014
Phase I Clinical Trial of the Mammalian Target of Rapamycin Inhibitor Everolimus in Combination With Oral Topotecan for Recurrent and Advanced Endometrial Cancer
Acevedo-Gadea C, Santin AD, Higgins SA, Urva S, Ratner E, Silasi DA, Azodi M, Rutherford T, Schwartz PE, Abu-Khalaf MM. Phase I Clinical Trial of the Mammalian Target of Rapamycin Inhibitor Everolimus in Combination With Oral Topotecan for Recurrent and Advanced Endometrial Cancer. International Journal Of Gynecological Cancer 2014, 24: 528-533. PMID: 24557436, DOI: 10.1097/igc.0000000000000085.Peer-Reviewed Original ResearchConceptsOral topotecanEndometrial cancerDay 1Pelvic external beam radiation therapyMammalian targetExternal beam radiation therapyPhase I clinical trialRecurrent endometrial cancerAdvanced endometrial cancerDose-limiting toxicityEfficacy of topotecanRapamycin inhibitor everolimusBeam radiation therapyOral everolimusStable diseaseVaginal brachytherapyMedian ageRapamycin inhibitorsInhibitor everolimusPreclinical dataClinical trialsMedian numberPharmacokinetic assessmentRadiation therapyEverolimus
2011
A phase I clinical trial of the mTOR inhibitor everolimus in combination with oral topotecan for patients with recurrent and advanced endometrial cancer
Abu-Khalaf M, Santin A, Ratner E, Silasi D, ElSahwi K, Baker L, Luther M, Azodi M, Rutherford T, Schwartz P. A phase I clinical trial of the mTOR inhibitor everolimus in combination with oral topotecan for patients with recurrent and advanced endometrial cancer. Gynecologic Oncology 2011, 120: s97-s98. DOI: 10.1016/j.ygyno.2010.12.232.Peer-Reviewed Original Research