2021
Programmed Death-Ligand 1 Tumor Proportion Score and Overall Survival From First-Line Pembrolizumab in Patients With Nonsquamous Versus Squamous NSCLC
Doroshow DB, Wei W, Gupta S, Zugazagoitia J, Robbins C, Adamson B, Rimm DL. Programmed Death-Ligand 1 Tumor Proportion Score and Overall Survival From First-Line Pembrolizumab in Patients With Nonsquamous Versus Squamous NSCLC. Journal Of Thoracic Oncology 2021, 16: 2139-2143. PMID: 34455068, PMCID: PMC8612948, DOI: 10.1016/j.jtho.2021.07.032.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntibodies, Monoclonal, HumanizedB7-H1 AntigenCarcinoma, Non-Small-Cell LungHumansImmune Checkpoint InhibitorsLung NeoplasmsProtein-Tyrosine KinasesProto-Oncogene ProteinsRetrospective StudiesConceptsPD-L1 tumor proportion scoreTumor proportion scoreHigh PD-L1 tumor proportion scoreOverall survivalNonsquamous histologySquamous NSCLCNonsquamous NSCLCPredictive biomarkersProportion scoreDeath ligand 1 (PD-L1) tumor proportion scoreElectronic health record-derived databaseFirst-line pembrolizumab therapyPD-1 expression levelsPD-L1 expression levelsCommunity oncology clinicsMedian OS differenceSingle-agent pembrolizumabImmune checkpoint inhibitorsImproved overall survivalMedian overall survivalPrimary end pointFirst-line pembrolizumabFirst-line therapyPD-L1 expressionPD-L1 testing
2020
Prospective multi-institutional evaluation of pathologist assessment of PD-L1 assays for patient selection in triple negative breast cancer
Reisenbichler ES, Han G, Bellizzi A, Bossuyt V, Brock J, Cole K, Fadare O, Hameed O, Hanley K, Harrison BT, Kuba MG, Ly A, Miller D, Podoll M, Roden AC, Singh K, Sanders MA, Wei S, Wen H, Pelekanou V, Yaghoobi V, Ahmed F, Pusztai L, Rimm DL. Prospective multi-institutional evaluation of pathologist assessment of PD-L1 assays for patient selection in triple negative breast cancer. Modern Pathology 2020, 33: 1746-1752. PMID: 32300181, PMCID: PMC8366569, DOI: 10.1038/s41379-020-0544-x.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, Monoclonal, HumanizedAntineoplastic AgentsB7-H1 AntigenBiomarkers, TumorFemaleHumansImmunohistochemistryPatient SelectionProspective StudiesReproducibility of ResultsTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerNegative breast cancerOverall percent agreementPD-L1Intraclass correlation coefficientBreast cancerAdvanced triple-negative breast cancerPD-L1 positive casesImmune cell stainingMultiple pathologistsPD-L1 scoringMulti-institutional evaluationLung cancer studiesAtezolizumab therapySP142 assaySP263 assaysPatient selectionSP263SP142US FoodDrug AdministrationPathologist's assessmentPositive casesReal-world settingPercent agreement
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
2017
Nuclear IRF-1 expression as a mechanism to assess “Capability” to express PD-L1 and response to PD-1 therapy in metastatic melanoma
Smithy JW, Moore LM, Pelekanou V, Rehman J, Gaule P, Wong PF, Neumeister VM, Sznol M, Kluger HM, Rimm DL. Nuclear IRF-1 expression as a mechanism to assess “Capability” to express PD-L1 and response to PD-1 therapy in metastatic melanoma. Journal For ImmunoTherapy Of Cancer 2017, 5: 25. PMID: 28331615, PMCID: PMC5359951, DOI: 10.1186/s40425-017-0229-2.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedB7-H1 AntigenBiomarkers, PharmacologicalDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticHumansImmunotherapyInterferon Regulatory Factor-1IpilimumabMaleMelanomaMiddle AgedNeoplasm MetastasisNeoplasms, Second PrimaryNivolumabProgrammed Cell Death 1 ReceptorConceptsProgression-free survivalObjective radiographic responsePD-L1 expressionPD-L1IRF-1 expressionMetastatic melanomaAnti-PD-1 therapyCombination ipilimumab/nivolumabHigh PD-L1 expressionAnti-PD-1 immunotherapyYale-New Haven HospitalIpilimumab/nivolumabPD-1 therapyPR/CRPre-treatment formalinRECIST v1.1 criteriaDeath ligand 1Valuable predictive biomarkerMajor unmet needNew Haven HospitalInterferon regulatory factor 1Combination ipilimumabProgressive diseaseRadiographic responseComplete responseObjective, domain-specific HER2 measurement in uterine and ovarian serous carcinomas and its clinical significance
Carvajal-Hausdorf DE, Schalper KA, Bai Y, Black J, Santin AD, Rimm DL. Objective, domain-specific HER2 measurement in uterine and ovarian serous carcinomas and its clinical significance. Gynecologic Oncology 2017, 145: 154-158. PMID: 28196634, PMCID: PMC5941302, DOI: 10.1016/j.ygyno.2017.02.002.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAfatinibAntibodies, Monoclonal, HumanizedAntineoplastic AgentsCohort StudiesExtracellular SpaceFemaleFluorescent Antibody TechniqueHumansIntracellular SpaceLapatinibMaytansineMiddle AgedNeoplasms, Cystic, Mucinous, and SerousOvarian NeoplasmsProtein DomainsQuinazolinesReceptor, ErbB-2Retrospective StudiesTissue Array AnalysisTrastuzumabUterine NeoplasmsConceptsUterine serous carcinomaOvarian serous carcinomaHER2 intracellular domainSerous carcinomaECD levelsECD statusTissue microarrayHER2 measurementQuantitative immunofluorescenceHER2 overexpression/amplificationClinico-pathologic characteristicsClinico-pathological featuresHER2-targeted agentsIntracellular domainOverexpression/amplificationHER2 extracellular domainExtracellular domainOSC patientsClinical trialsBreast cancerClinical significancePatientsHER2 assaysP95-HER2Carcinoma
2015
Measurement of Domain-Specific HER2 (ERBB2) Expression May Classify Benefit From Trastuzumab in Breast Cancer
Carvajal-Hausdorf DE, Schalper KA, Pusztai L, Psyrri A, Kalogeras KT, Kotoula V, Fountzilas G, Rimm DL. Measurement of Domain-Specific HER2 (ERBB2) Expression May Classify Benefit From Trastuzumab in Breast Cancer. Journal Of The National Cancer Institute 2015, 107: djv136. PMID: 25991002, PMCID: PMC4554192, DOI: 10.1093/jnci/djv136.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsChemotherapy, AdjuvantClinical Trials as TopicDisease-Free SurvivalExtracellular SpaceFemaleFluorescent Antibody TechniqueGene Expression Regulation, NeoplasticHumansIntracellular SpaceKaplan-Meier EstimateMiddle AgedPredictive Value of TestsPrognosisReceptor, ErbB-2Sensitivity and SpecificityTissue Array AnalysisTrastuzumabTreatment OutcomeConceptsHuman epidermal growth factor receptor 2ECD expressionICD statusLonger DFSQuantitative immunofluorescenceTrastuzumab therapyPrognostic valueBreast cancerTissue microarrayEpidermal growth factor receptor 2Adjuvant trastuzumab therapyDisease-free survival analysisTrastuzumab-treated patientsGrowth factor receptor 2High positive predictive valueHER2-positive tumorsKaplan-Meier estimatesFactor receptor 2ERBB2 gene amplificationHER2 protein expressionPositive predictive valueExtracellular domainAdjuvant chemotherapyHER2-ICDBetter DFS
2014
EGFR expression is associated with decreased benefit from trastuzumab in the NCCTG N9831 (Alliance) trial
Cheng H, Ballman K, Vassilakopoulou M, Dueck AC, Reinholz MM, Tenner K, Gralow J, Hudis C, Davidson NE, Fountzilas G, McCullough AE, Chen B, Psyrri A, Rimm DL, Perez EA. EGFR expression is associated with decreased benefit from trastuzumab in the NCCTG N9831 (Alliance) trial. British Journal Of Cancer 2014, 111: 1065-1071. PMID: 25117817, PMCID: PMC4453859, DOI: 10.1038/bjc.2014.442.Peer-Reviewed Original ResearchConceptsNorth Central Cancer Treatment GroupMetastatic breast cancer cohortEpidermal growth factor receptorBreast cancer cohortHigh EGFR expressionEGFR expressionConcurrent trastuzumabGrowth factor receptorCancer cohortEGFR antibodyNCCTG N9831 trialsAnti-HER2 therapyCancer Treatment GroupDisease-free survivalFactor receptorN9831 trialsSequential trastuzumabAdditive therapyArm AClinical outcomesTreatment optionsWorse outcomesArm CTissue microarrayTreatment groupsInduction cetuximab, paclitaxel, and carboplatin followed by chemoradiation with cetuximab, paclitaxel, and carboplatin for stage III/IV head and neck squamous cancer: a phase II ECOG-ACRIN trial (E2303)
Wanebo HJ, Lee J, Burtness BA, Ridge JA, Ghebremichael M, Spencer SA, Psyrri D, Pectasides E, Rimm D, Rosen FR, Hancock MR, Tolba KA, Forastiere AA. Induction cetuximab, paclitaxel, and carboplatin followed by chemoradiation with cetuximab, paclitaxel, and carboplatin for stage III/IV head and neck squamous cancer: a phase II ECOG-ACRIN trial (E2303). Annals Of Oncology 2014, 25: 2036-2041. PMID: 25009013, PMCID: PMC4176450, DOI: 10.1093/annonc/mdu248.Peer-Reviewed Original ResearchConceptsEvent-free survivalStage III/IV headResponse/survivalInduction therapyComplete responseStage III/IV HNSCCNeck squamous cell carcinomaPrimary site biopsiesTreatment-related deathsPathologic complete responseNeck squamous cancerSquamous cell carcinomaProtein expression statusEligible patientsSite biopsiesOverall survivalCell carcinomaPromising survivalSquamous cancerDisease progressionChemoradiationRadiation therapyPatientsWeek 9CetuximabIn Situ Quantitative Measurement of HER2mRNA Predicts Benefit from Trastuzumab-Containing Chemotherapy in a Cohort of Metastatic Breast Cancer Patients
Vassilakopoulou M, Togun T, Dafni U, Cheng H, Bordeaux J, Neumeister VM, Bobos M, Pentheroudakis G, Skarlos DV, Pectasides D, Kotoula V, Fountzilas G, Rimm DL, Psyrri A. In Situ Quantitative Measurement of HER2mRNA Predicts Benefit from Trastuzumab-Containing Chemotherapy in a Cohort of Metastatic Breast Cancer Patients. PLOS ONE 2014, 9: e99131. PMID: 24968015, PMCID: PMC4072595, DOI: 10.1371/journal.pone.0099131.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBiomarkers, TumorBreast NeoplasmsCohort StudiesFemaleHumansMiddle AgedNeoplasm MetastasisReceptor, ErbB-2RNA, MessengerTrastuzumabTreatment OutcomeConceptsBreast cancer patientsMetastatic breast cancer patientsFISH HER2Cancer patientsHER2 mRNAPrognostic factorsTrastuzumab-treated metastatic breast cancer patientsMultivariate Cox regression modelECD HER2Log rank pMetastatic breast cancerStrong prognostic factorCox regression modelKaplan-Meier estimatesHER2 mRNA levelsHER2-ICDChemotherapy regimensMetastatic cohortTrastuzumab treatmentBreast cancerTissue microarrayMRNA statusPerformance of markersHER2 receptorPredictive valuePrognostic Biomarkers in Phase II Trial of Cetuximab-Containing Induction and Chemoradiation in Resectable HNSCC: Eastern Cooperative Oncology Group E2303
Psyrri A, Lee JW, Pectasides E, Vassilakopoulou M, Kosmidis EK, Burtness BA, Rimm DL, Wanebo HJ, Forastiere AA. Prognostic Biomarkers in Phase II Trial of Cetuximab-Containing Induction and Chemoradiation in Resectable HNSCC: Eastern Cooperative Oncology Group E2303. Clinical Cancer Research 2014, 20: 3023-3032. PMID: 24700741, PMCID: PMC4049169, DOI: 10.1158/1078-0432.ccr-14-0113.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarboplatinCarcinoma, Squamous CellCetuximabChemoradiotherapyDisease-Free SurvivalDrug Resistance, NeoplasmFemaleFluorescent Antibody TechniqueHead and Neck NeoplasmsHumansInduction ChemotherapyKaplan-Meier EstimateMaleMiddle AgedMitogen-Activated Protein Kinase KinasesPaclitaxelPhosphatidylinositol 3-KinasesPrognosisProportional Hazards ModelsProto-Oncogene Proteins c-aktRas ProteinsSignal TransductionSquamous Cell Carcinoma of Head and NeckTissue Array AnalysisConceptsProgression-free survivalEvent-free survivalPhase II trialOverall survivalII trialTissue microarrayStage III/IV headMultivariable Cox proportional hazards modelsMultivariable Cox regression analysisNeck squamous cell cancerRAS/MAPK/ERKCox proportional hazards modelInsulin-like growth factor 1 receptorLarge prospective studiesCox regression analysisInferior overall survivalKaplan-Meier methodSquamous cell cancerLog-rank testGrowth factor 1 receptorProportional hazards modelPI3K/Akt pathwayFactor 1 receptorPI3K/AktEGF receptorQuantitative measurements of HER2 and phospho-HER2 expression: correlation with pathologic response to neoadjuvant chemotherapy and trastuzumab
Cheng H, Bai Y, Sikov W, Sinclair N, Bossuyt V, Abu-Khalaf MM, Harris LN, Rimm DL. Quantitative measurements of HER2 and phospho-HER2 expression: correlation with pathologic response to neoadjuvant chemotherapy and trastuzumab. BMC Cancer 2014, 14: 326. PMID: 24885187, PMCID: PMC4037428, DOI: 10.1186/1471-2407-14-326.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAlbuminsAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsCarboplatinChemotherapy, AdjuvantConnecticutFemaleFluorescent Antibody TechniqueHumansNeoadjuvant TherapyPaclitaxelPhosphorylationProteomicsReceptor, ErbB-2Rhode IslandTime FactorsTrastuzumabTreatment OutcomeConceptsLikelihood of responsePhospho-HER2Nab-paclitaxelPathologic responseHER2 levelsAdvanced HER2-positive breast cancerHER2-positive breast cancerCarboplatin combination therapyPreoperative clinical trialPre-surgical settingSingle-agent trastuzumabPathologic complete responseInitiation of treatmentWeeks of treatmentBreast cancer patientsTumor core biopsiesCore biopsy samplesMonoclonal antibody trastuzumabEvaluable patientsNeoadjuvant regimenNeoadjuvant chemotherapyNeoadjuvant therapyNeoadjuvant treatmentComplete responsePreoperative setting
2008
Comparison of quantitative immunofluorescence with conventional methods for HER2/neu testing with respect to response to trastuzumab therapy in metastatic breast cancer.
Giltnane JM, Molinaro A, Cheng H, Robinson A, Turbin D, Gelmon K, Huntsman D, Rimm DL. Comparison of quantitative immunofluorescence with conventional methods for HER2/neu testing with respect to response to trastuzumab therapy in metastatic breast cancer. Archives Of Pathology & Laboratory Medicine 2008, 132: 1635-47. PMID: 18834223, DOI: 10.5858/2008-132-1635-coqiwc.Peer-Reviewed Original ResearchAnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBreast NeoplasmsCell LineCricetinaeFemaleHumansImmunohistochemistryIn Situ Hybridization, FluorescenceLogistic ModelsMiddle AgedPredictive Value of TestsReceptor, ErbB-2Retrospective StudiesSensitivity and SpecificityTissue Array AnalysisTrastuzumabTreatment Outcome