2023
Molecular determinants of clinical outcomes of pembrolizumab in recurrent ovarian cancer: Exploratory analysis of KEYNOTE-100
Ledermann J, Shapira-Frommer R, Santin A, Lisyanskaya A, Pignata S, Vergote I, Raspagliesi F, Sonke G, Birrer M, Provencher D, Sehouli J, Colombo N, González-Martín A, Oaknin A, Ottevanger P, Rudaitis V, Kobie J, Nebozhyn M, Edmondson M, Sun Y, Cristescu R, Jelinic P, Keefe S, Matulonis U. Molecular determinants of clinical outcomes of pembrolizumab in recurrent ovarian cancer: Exploratory analysis of KEYNOTE-100. Gynecologic Oncology 2023, 178: 119-129. PMID: 37862791, DOI: 10.1016/j.ygyno.2023.09.012.Peer-Reviewed Original Research
2020
First-in-Human, Multicenter, Phase I Dose-Escalation and Expansion Study of Anti-Mesothelin Antibody–Drug Conjugate Anetumab Ravtansine in Advanced or Metastatic Solid Tumors
Hassan R, Blumenschein GR, Moore KN, Santin AD, Kindler HL, Nemunaitis JJ, Seward SM, Thomas A, Kim SK, Rajagopalan P, Walter AO, Laurent D, Childs BH, Sarapa N, Elbi C, Bendell JC. First-in-Human, Multicenter, Phase I Dose-Escalation and Expansion Study of Anti-Mesothelin Antibody–Drug Conjugate Anetumab Ravtansine in Advanced or Metastatic Solid Tumors. Journal Of Clinical Oncology 2020, 38: 1824-1835. PMID: 32213105, PMCID: PMC7255978, DOI: 10.1200/jco.19.02085.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, ImmunologicalFemaleGPI-Linked ProteinsHumansImmunoconjugatesMaleMaximum Tolerated DoseMaytansineMesothelinMiddle AgedNeoplasm MetastasisNeoplasm Recurrence, LocalNeoplasmsProgression-Free SurvivalConceptsAnetumab ravtansineDose-escalation cohortsMetastatic solid tumorsAnti-mesothelin antibodySolid tumorsExpansion cohortClinical activityCommon drug-related adverse eventsDrug-related adverse eventsPhase I Dose-EscalationMultiple solid tumor typesPhase IDose-expansion studyI Dose-EscalationPeripheral sensory neuropathyPhase II studyRecurrent ovarian cancerRecurrent solid tumorsPreliminary antitumor activityDrug-related deathsFavorable pharmacokinetic profileSolid tumor typesAntibody-drug conjugatesStable diseaseAdult patientsTargeting human epidermal growth factor receptor 2 (HER2) in gynecologic malignancies.
Erickson BK, Zeybek B, Santin AD, Fader AN. Targeting human epidermal growth factor receptor 2 (HER2) in gynecologic malignancies. Current Opinion In Obstetrics & Gynecology 2020, 32: 57-64. PMID: 31833974, PMCID: PMC7307693, DOI: 10.1097/gco.0000000000000599.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalBiomarkers, TumorCystadenocarcinoma, SerousFemaleHumansMolecular Targeted TherapyRandomized Controlled Trials as TopicReceptor, ErbB-2TrastuzumabUterine NeoplasmsConceptsHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Growth factor receptor 2Uterine serous carcinomaGynecologic malignanciesFactor receptor 2Serous carcinomaReceptor 2Recurrent uterine serous carcinomaAnti-HER2 antibody trastuzumabHER2-positive diseaseAnti-HER2 therapyAnti-HER2 treatmentHER2-positive breastTrial of womenEndometrial cancer subtypesMore treatment optionsEffective therapeutic targetTreatment optionsUterine carcinosarcomaTrastuzumab efficacyHER2 amplificationTargeted therapyGastric cancerSignificant efficacyPhase II evaluation of nivolumab in the treatment of persistent or recurrent cervical cancer (NCT02257528/NRG-GY002)
Santin AD, Deng W, Frumovitz M, Buza N, Bellone S, Huh W, Khleif S, Lankes HA, Ratner ES, O'Cearbhaill RE, Jazaeri AA, Birrer M. Phase II evaluation of nivolumab in the treatment of persistent or recurrent cervical cancer (NCT02257528/NRG-GY002). Gynecologic Oncology 2020, 157: 161-166. PMID: 31924334, PMCID: PMC7127981, DOI: 10.1016/j.ygyno.2019.12.034.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, ImmunologicalB7-H1 AntigenFemaleHumansMiddle AgedNeoplasm Recurrence, LocalNivolumabProgression-Free SurvivalUterine Cervical NeoplasmsYoung AdultConceptsTreatment-related adverse eventsRecurrent cervical cancerPD-L1 expressionPlatinum-based chemotherapyCervical cancerStable diseaseGrade 3 treatment-related adverse eventsGrade 4 treatment-related adverse eventsGrade 5 treatment-related adverse eventsECOG PS 0Prior systemic therapyRecurrent cervical carcinomaResponse/toxicitySingle-agent nivolumabSystemic chemotherapy regimenTolerability of nivolumabImmune checkpoint inhibitorsPercent of patientsAcceptable safety profilePhase II trialKey eligibility criteriaPhase II evaluationECOG PSNivolumab 3RECIST 1.1
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 study
2018
Exceptional Response to Pembrolizumab in a Metastatic, Chemotherapy/Radiation-Resistant Ovarian Cancer Patient Harboring a PD-L1-Genetic Rearrangement
Bellone S, Buza N, Choi J, Zammataro L, Gay L, Elvin J, Rimm DL, Liu Y, Ratner E, Schwartz PE, Santin AD. Exceptional Response to Pembrolizumab in a Metastatic, Chemotherapy/Radiation-Resistant Ovarian Cancer Patient Harboring a PD-L1-Genetic Rearrangement. Clinical Cancer Research 2018, 24: 3282-3291. PMID: 29351920, PMCID: PMC6050068, DOI: 10.1158/1078-0432.ccr-17-1805.Peer-Reviewed Original ResearchMeSH KeywordsAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorBiopsyComputational BiologyDrug Resistance, NeoplasmExome SequencingFemaleGene RearrangementHLA AntigensHumansMolecular Targeted TherapyMutationOvarian NeoplasmsPositron Emission Tomography Computed TomographyProgrammed Cell Death 1 ReceptorReceptors, Cell SurfaceRetreatmentT-LymphocytesTreatment OutcomeConceptsImmune checkpoint inhibitor pembrolizumabCheckpoint inhibitor pembrolizumabComplete clinical responseClinical responsePD-L1Ovarian carcinomaAberrant PD-L1 expressionPD-L1 surface expressionAnti-PD1 inhibitorsPD-L1 expressionRemarkable clinical responsesHigh-grade ovarian carcinomaStandard treatment modalityAlternative therapeutic optionClear cell featuresNovel treatment optionsSignificant side effectsT-cell lymphocytesWhole exome sequencing techniqueClin Cancer ResMetastatic human tumorsRecurrent diseaseComplete responseHeavy infiltrationTherapeutic options