2024
Contribution of tumour and immune cells to PD‐L1 expression as a predictive biomarker in metastatic triple‐negative breast cancer: exploratory analysis from KEYNOTE‐119
Cortes J, Winer E, Lipatov O, Im S, Gonçalves A, Muñoz‐Couselo E, Lee K, Schmid P, Tamura K, Testa L, Witzel I, Ohtani S, Hund S, Kulangara K, Karantza V, Mejia J, Ma J, Jelinic P, Huang L, Pruitt S, Emancipator K. Contribution of tumour and immune cells to PD‐L1 expression as a predictive biomarker in metastatic triple‐negative breast cancer: exploratory analysis from KEYNOTE‐119. The Journal Of Pathology Clinical Research 2024, 10: e12371. PMID: 38627977, PMCID: PMC11021797, DOI: 10.1002/2056-4538.12371.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerPD-L1 expressionTriple-negative breast cancerPD-L1 CPSPD-L1Breast cancerTreated metastatic triple-negative breast cancerIncreased programmed death ligand 1PD-L1 IHC 22C3 pharmDxEfficacy of pembrolizumab monotherapyPD-L1 expression assessmentProgrammed death-1 blockadeExpression of PD-L1Objective response rateProgression-free survivalTumor proportion scoreDeath-ligand 1Contribution of tumorImmune cell densityReceiver operating characteristic curveArea under the receiver operating characteristic curvePredictive of responsePembrolizumab monotherapyOverall survivalUniform scoring system
2023
Impact of pembrolizumab versus chemotherapy on health-related quality of life in patients with metastatic triple-negative breast cancer: results from the phase 3 randomised KEYNOTE-119 study
Schmid P, Lipatov O, Im S, Goncalves A, Muñoz-Couselo E, Lee K, Tamura K, Testa L, Witzel I, Ohtani S, Turner N, Zambelli S, Harbeck N, Andre F, Dent R, Mejia J, Zhou X, Haiderali A, Nguyen A, Cortes J, Winer E. Impact of pembrolizumab versus chemotherapy on health-related quality of life in patients with metastatic triple-negative breast cancer: results from the phase 3 randomised KEYNOTE-119 study. European Journal Of Cancer 2023, 195: 113393. PMID: 37976633, DOI: 10.1016/j.ejca.2023.113393.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerCombined positive scoreMetastatic triple-negative breast cancerPD-L1 combined positive scoreHealth-related qualityBreast cancerQLQ-C30 functional scalesTumor PD-L1 expressionGHS/QoLNausea/vomitingPD-L1 expressionStart of treatmentHRQoL resultsEligible patientsHRQoL analysisOverall survivalSystemic therapyClinical outcomesFunctional scalesPhysician's choicePatientsChemotherapyFirst onsetCountry guidelinesMedian TTD
2021
Saci-IO HR+: Randomized phase II trial of sacituzumab govitecan (SG) +/- pembrolizumab in PD-L1+ hormone receptor-positive (HR+) / HER2- metastatic breast cancer (MBC).
Garrido-Castro A, Keenan T, Li T, Lange P, Callahan C, Guerriero J, Tayob N, Anderson L, Stover D, Gogineni K, Carey L, Nanda R, Winer E, Mittendorf E, Tolaney S. Saci-IO HR+: Randomized phase II trial of sacituzumab govitecan (SG) +/- pembrolizumab in PD-L1+ hormone receptor-positive (HR+) / HER2- metastatic breast cancer (MBC). Journal Of Clinical Oncology 2021, 39: tps1102-tps1102. DOI: 10.1200/jco.2021.39.15_suppl.tps1102.Peer-Reviewed Original ResearchProgression-free survivalImmune checkpoint inhibitorsMedian progression-free survivalRandomized phase II trialCombined positive scorePhase II trialSacituzumab govitecanII trialPD-L1Anti-PD-1/L1 antibodyPD-1/L1 inhibitorsHER2- metastatic breast cancerAntibody-dependent cellular cytotoxicityT cell effector functionPrior hormonal therapyPD-L1 expressionAntitumor immune responseChronic antigen stimulationHealth-related qualityKey eligibility criteriaRegulatory T cellsT cell dysfunctionCell effector functionsOne-sided alphaImmune cell receptorsSaci-IO TNBC: Randomized phase II trial of sacituzumab govitecan (SG) +/- pembrolizumab in PD-L1– metastatic triple-negative breast cancer (mTNBC).
Garrido-Castro A, Keenan T, Li T, Lange P, Callahan C, Guerriero J, Tayob N, Anderson L, Yam C, Daniel B, Carey L, Nanda R, Winer E, Mittendorf E, Tolaney S. Saci-IO TNBC: Randomized phase II trial of sacituzumab govitecan (SG) +/- pembrolizumab in PD-L1– metastatic triple-negative breast cancer (mTNBC). Journal Of Clinical Oncology 2021, 39: tps1106-tps1106. DOI: 10.1200/jco.2021.39.15_suppl.tps1106.Peer-Reviewed Original ResearchMetastatic triple-negative breast cancerProgression-free survivalImmune checkpoint inhibitorsMedian progression-free survivalRandomized phase II trialPhase II trialSacituzumab govitecanPD-L1II trialImmune cellsBreast cancerAnti-PD-1/L1 antibodyPD-1/L1 inhibitorsAntibody-dependent cellular cytotoxicityT cell effector functionTriple-negative breast cancerPrior systemic therapyPD-L1 expressionAntitumor immune responseChronic antigen stimulationHealth-related qualityKey eligibility criteriaRegulatory T cellsT cell dysfunctionCell effector functions
2019
37O Subgroup analysis of IMpassion130: Atezolizumab + nab-paclitaxel (nab-P) in patients (pts) with advanced triple-negative breast cancer (TNBC) in Asian countries
Iwata H, Im S, Sohn J, Jung K, Im Y, Lee K, Inoue K, Tamura K, Wong A, Emens L, Barrios C, Adams S, Schneeweiss A, Diéras V, Winer E, Chui S, Henschel V, Rugo H, Loi S, Schmid P. 37O Subgroup analysis of IMpassion130: Atezolizumab + nab-paclitaxel (nab-P) in patients (pts) with advanced triple-negative breast cancer (TNBC) in Asian countries. Annals Of Oncology 2019, 30: ix13-ix14. DOI: 10.1093/annonc/mdz418.Peer-Reviewed Original ResearchTriple-negative breast cancerAdvanced triple-negative breast cancerGenentech/RochePD-L1 expressionPD-L1Bristol-Myers SquibbF. Hoffmann-La RocheDaiichi SankyoBoehringer IngelheimHoffmann-La RocheSeattle GeneticsRoche/GenentechTumor-infiltrating immune cellsBreast Cancer Research FoundationECOG PS 0Key secondary endpointPD-L1 positivityNew safety signalsPD-L1 testingCo-primary endpointsEli LillyCancer Research FoundationNational Cancer InstituteMedical writing assistanceMedical Research CouncilA phase II study of pembrolizumab in combination with palliative radiotherapy (RT) for hormone receptor-positive (HR+) metastatic breast cancer (MBC).
Barroso-Sousa R, Krop I, Trippa L, Tan-Wasielewski Z, Li T, Osmani W, Andrews C, Dillon D, Richardson E, Winer E, Mittendorf E, Schoenfeld J, Tolaney S. A phase II study of pembrolizumab in combination with palliative radiotherapy (RT) for hormone receptor-positive (HR+) metastatic breast cancer (MBC). Journal Of Clinical Oncology 2019, 37: 1047-1047. DOI: 10.1200/jco.2019.37.15_suppl.1047.Peer-Reviewed Original ResearchMetastatic breast cancerNeutrophil/lymphocyte ratioObjective response rateProgression-free survivalTumor-infiltrating lymphocytesPalliative radiotherapyAdverse eventsHormone receptor-positive metastatic breast cancerPhase II single-arm studyMedian progression-free survivalCause adverse eventsDistant tumor responsesECOG PS 1Prior cytotoxic therapyImmune checkpoint inhibitorsPD-L1 expressionPD-L1 statusPhase II studySingle-arm studyTotal RT doseUnexpected adverse eventsECOG PSEligible ptsRECIST v1.1Measurable lesionsThe immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial
Barroso-Sousa R, Barry WT, Guo H, Dillon D, Tan YB, Fuhrman K, Osmani W, Getz A, Baltay M, Dang C, Yardley D, Moy B, Marcom PK, Mittendorf EA, Krop IE, Winer EP, Tolaney SM. The immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial. Annals Of Oncology 2019, 30: 575-581. PMID: 30753274, PMCID: PMC8033534, DOI: 10.1093/annonc/mdz047.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBiomarkers, TumorBreastBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalFemaleFollow-Up StudiesHumansKaplan-Meier EstimateMastectomyMiddle AgedPaclitaxelReceptor, ErbB-2TrastuzumabTumor BurdenTumor MicroenvironmentConceptsHER2-positive breast cancerSmall HER2-positive breast cancersImmune gene signaturesBreast cancerImmune profileAPT trialPD-L1Immune markersImmune microenvironmentSmall HER2-positive tumorsStromal PD-L1 expressionNode-negative breast cancerCell signatureGene signatureHuman epidermal growth factor receptorStromal PD-L1PD-L1 expressionHistological grade 2Luminal B tumorsB cell signaturesBreast cancer trialsHER2-positive tumorsImmune cell signaturesBasal-like tumorsHistological grade 1
2017
Immune biomarkers and treatment (tx) outcome in hormone receptor-positive (HR+) breast cancer (BC) patients (pts) treated with preoperative chemotherapy (preop chemo) plus bevacizumab (bev).
Waks A, Barry W, Gjini E, Dillon D, Rodig S, Brock J, Baltay M, Savoie J, Stover D, Winer E, Krop I, Tolaney S. Immune biomarkers and treatment (tx) outcome in hormone receptor-positive (HR+) breast cancer (BC) patients (pts) treated with preoperative chemotherapy (preop chemo) plus bevacizumab (bev). Journal Of Clinical Oncology 2017, 35: e12134-e12134. DOI: 10.1200/jco.2017.35.15_suppl.e12134.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesTPD-L1Miller-PaynePathologic responseImmune biomarkersHormone receptor-positive breast cancer patientsReceptor-positive breast cancer patientsPanCancer Immune Profiling PanelResidual cancer burden scorePathologic complete responsePD-L1 expressionBreast cancer patientsPD-L1 scoresImmune Profiling PanelImportant clinical implicationsPreoperative chemotherapyComplete responseProspective trialTumor-immune interactionsBurden scoreCancer patientsImmune microenvironmentUnadjusted analysesTumor gradeTreatment outcomesPhase 2 study of pembrolizumab (pembro) monotherapy for previously treated metastatic triple-negative breast cancer (mTNBC): KEYNOTE-086 cohort A.
Adams S, Schmid P, Rugo H, Winer E, Loirat D, Awada A, Cescon D, Iwata H, Campone M, Nanda R, Hui R, Curigliano G, Toppmeyer D, O'Shaughnessy J, Loi S, Paluch-Shimon S, Card D, Zhao J, Karantza V, Cortes J. Phase 2 study of pembrolizumab (pembro) monotherapy for previously treated metastatic triple-negative breast cancer (mTNBC): KEYNOTE-086 cohort A. Journal Of Clinical Oncology 2017, 35: 1008-1008. DOI: 10.1200/jco.2017.35.15_suppl.1008.Peer-Reviewed Original ResearchMetastatic triple-negative breast cancerTreatment-related AEsPD-L1 expressionPD-L1Manageable safetyTriple-negative breast cancerECOG PS 0Subset of ptsDisease control ratePhase 2 studyPoor prognostic factorEfficacy/safetyBest overall responseCohort A.Evaluable ptsKEYNOTE-012Median DoRMedian PFSPrior chemotherapyData cutoffPembrolizumab monotherapyDurable responsesMetastatic diseasePrior linesPS 0