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
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 analysisChemotherapy
2022
Lenvatinib 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
A phase 2 evaluation of pembrolizumab for recurrent Lynch‐like versus sporadic endometrial cancers with microsatellite instability
Bellone S, Roque DM, Siegel ER, Buza N, Hui P, Bonazzoli E, Guglielmi A, Zammataro L, Nagarkatti N, Zaidi S, Lee J, Silasi D, Huang GS, Andikyan V, Damast S, Clark M, Azodi M, Schwartz PE, Tymon‐Rosario J, Harold JA, Mauricio D, Zeybek B, Menderes G, Altwerger G, Ratner E, Alexandrov LB, Iwasaki A, Kong Y, Song E, Dong W, Elvin JA, Choi J, Santin AD. A phase 2 evaluation of pembrolizumab for recurrent Lynch‐like versus sporadic endometrial cancers with microsatellite instability. Cancer 2021, 128: 1206-1218. PMID: 34875107, PMCID: PMC9465822, DOI: 10.1002/cncr.34025.Peer-Reviewed Original ResearchConceptsObjective response rateImmune checkpoint inhibitorsProgression-free survivalEndometrial cancerWhole-exome sequencingSporadic endometrial cancerOverall survivalEnd pointPhase 2 pilot studyPrimary end pointSecondary end pointsTumor mutation burdenPhase 2 evaluationLarger confirmatory studiesAntigen processing/presentationProcessing/presentationCheckpoint inhibitorsSurgical resectionICI resistanceDMMR patientsPrognostic significanceDMMR tumorsMechanisms of resistanceLocal treatmentSporadic MSIA 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 burdenPatients
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