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
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 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 choice
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 MSIO008/#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 PSA 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 burdenPatientsSacituzumab 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 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 chemotherapyTROPiCS–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 inhibitor
2019
Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study
Matulonis UA, Shapira-Frommer R, Santin AD, Lisyanskaya AS, Pignata S, Vergote I, Raspagliesi F, Sonke GS, Birrer M, Provencher DM, Sehouli J, Colombo N, González-Martín A, Oaknin A, Ottevanger PB, Rudaitis V, Katchar K, Wu H, Keefe S, Ruman J, Ledermann JA. Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study. Annals Of Oncology 2019, 30: 1080-1087. PMID: 31046082, DOI: 10.1093/annonc/mdz135.Peer-Reviewed Original ResearchConceptsRecurrent ovarian cancerObjective response rateDisease control rateProgression-free survivalTreatment-free intervalDuration of responseAdvanced recurrent ovarian cancerPD-L1 expressionPlatinum-free intervalCohort AOverall survivalPrior linesCohort BOvarian cancerHigh PD-L1 expressionLow objective response rateMedian DORSolid Tumors version 1.1End pointGynecologic cancer-related deathBlinded independent central reviewSafety of pembrolizumabSingle-agent pembrolizumabMedian overall survivalPhase II studySacituzumab 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
2015
Weekly ixabepilone with or without biweekly bevacizumab in the treatment of recurrent or persistent uterine and ovarian/primary peritoneal/fallopian tube cancers: A retrospective review
Roque DM, Ratner ES, Silasi DA, Azodi M, Rutherford TJ, Schwartz PE, Nelson WK, Santin AD. Weekly ixabepilone with or without biweekly bevacizumab in the treatment of recurrent or persistent uterine and ovarian/primary peritoneal/fallopian tube cancers: A retrospective review. Gynecologic Oncology 2015, 137: 392-400. PMID: 25792179, DOI: 10.1016/j.ygyno.2015.03.008.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabDisease-Free SurvivalDrug Administration ScheduleEpothilonesFallopian Tube NeoplasmsFemaleHumansMiddle AgedNeoplasm Recurrence, LocalOvarian NeoplasmsPeritoneal NeoplasmsProspective StudiesRetrospective StudiesConceptsObjective response rateFallopian tube cancerWeekly ixabepiloneOvarian cancerConcurrent bevacizumabRetrospective reviewMedian PFS/OSSimilar objective response ratesWarrants further prospective studySingle-institution retrospective reviewCA-125 criteriaPFS/OSTreatment of recurrentKaplan-Meier methodFurther prospective studiesBiweekly bevacizumabMedian PFSAcceptable toxicityGrade 1/2Median durationOverall survivalPrior linesClinical outcomesProspective studyUterine cancer