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
Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial
Winer EP, Lipatov O, Im SA, Goncalves A, Muñoz-Couselo E, Lee KS, Schmid P, Tamura K, Testa L, Witzel I, Ohtani S, Turner N, Zambelli S, Harbeck N, Andre F, Dent R, Zhou X, Karantza V, Mejia J, Cortes J, investigators K. Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial. The Lancet Oncology 2021, 22: 499-511. PMID: 33676601, DOI: 10.1016/s1470-2045(20)30754-3.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerTriple-negative breast cancerCombined positive scoreMedian overall survivalPD-L1 combined positive scoreTreatment-related adverse eventsPhase 3 trialChemotherapy groupOverall survivalPembrolizumab groupBreast cancerAdverse eventsPrimary endpointMetastatic diseaseEastern Cooperative Oncology Group performance statusPD-L1 tumor statusCommon grade 3Durable antitumour activityInvestigator-choice chemotherapyPrevious systemic treatmentSerious adverse eventsThird-line treatmentSubpopulation of patientsTreatment of patientsSingle-drug chemotherapy
2020
A phase Ib study of pembrolizumab (pembro) plus trastuzumab emtansine (T-DM1) for metastatic HER2+ breast cancer (MBC).
Waks A, Keenan T, Li T, Tayob N, Wulf G, Richardson E, Mittendorf E, Overmoyer B, Krop I, Winer E, Van Allen E, Agudo J, Tolaney S. A phase Ib study of pembrolizumab (pembro) plus trastuzumab emtansine (T-DM1) for metastatic HER2+ breast cancer (MBC). Journal Of Clinical Oncology 2020, 38: 1046-1046. DOI: 10.1200/jco.2020.38.15_suppl.1046.Peer-Reviewed Original ResearchObjective response rateProgression-free survivalAdverse eventsT-DM1PD-L1 combined positive scoreTumor-infiltrating lymphocyte (TIL) statusClinical benefit rateDose-finding cohortMedian age 54Phase 2 dosePhase Ib studyCombined positive scoreAnti-PD1 antibodyPhase 1 trialDe-escalation designEligible patientsLymphocyte statusMetastatic HER2Expansion cohortOral mucositisPrimary endpointSecondary endpointsAntitumor immunityImmune signaturesPrior lines
2019
LBA21 KEYNOTE-119: Phase III study of pembrolizumab (pembro) versus single-agent chemotherapy (chemo) for metastatic triple negative breast cancer (mTNBC)
Cortés J, Lipatov O, Im S, Gonçalves A, Lee K, Schmid P, Tamura K, Testa L, Witzel I, Ohtani S, Zambelli S, Harbeck N, André F, Dent R, Zhou X, Karantza V, Mejia J, Winer E. LBA21 KEYNOTE-119: Phase III study of pembrolizumab (pembro) versus single-agent chemotherapy (chemo) for metastatic triple negative breast cancer (mTNBC). Annals Of Oncology 2019, 30: v859-v860. DOI: 10.1093/annonc/mdz394.010.Peer-Reviewed Original ResearchMetastatic triple-negative breast cancerCombined positive scoreSubsidiary of MerckGerman Study GroupDohme Corp.Merck SharpSeattle GeneticsGrade 3Study groupOpen-label phase III studyPD-L1 combined positive scoreEnd pointTriple-negative breast cancerDaiichi SankyoF. Hoffman-La RochePrior systemic treatmentPrimary end pointSecondary end pointsSingle-agent chemotherapyPhase III studyHigh-grade toxicityNegative breast cancerPD-L1 enrichmentTreatment effectsBristol-Myers SquibbPembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 study
Adams S, Loi S, Toppmeyer D, Cescon DW, De Laurentiis M, Nanda R, Winer EP, Mukai H, Tamura K, Armstrong A, Liu MC, Iwata H, Ryvo L, Wimberger P, Rugo HS, Tan AR, Jia L, Ding Y, Karantza V, Schmid P. Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 study. Annals Of Oncology 2019, 30: 405-411. PMID: 30475947, DOI: 10.1093/annonc/mdy518.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerPositive metastatic triple-negative breast cancerTreatment-related adverse eventsTriple-negative breast cancerDisease control rateObjective response rateFirst-line therapyProgression-free survivalAdverse eventsPD-L1Stable diseasePembrolizumab monotherapyOverall survivalCohort BControl rateBreast cancerResponse ratePD-L1 combined positive scoreCentral nervous system metastasesGrade 4 adverse eventsMedian progression-free survivalStandard first-line treatmentEnd pointGrade 3 severityManageable safety profile
2017
Phase 2 study of pembrolizumab as first-line therapy for PD-L1–positive metastatic triple-negative breast cancer (mTNBC): Preliminary data from KEYNOTE-086 cohort B.
Adams S, Loi S, Toppmeyer D, Cescon D, De Laurentiis M, Nanda R, Winer E, Mukai H, Tamura K, Armstrong A, Liu M, Iwata H, Ryvo L, Wimberger P, Card D, Ding Y, Karantza V, Schmid P. Phase 2 study of pembrolizumab as first-line therapy for PD-L1–positive metastatic triple-negative breast cancer (mTNBC): Preliminary data from KEYNOTE-086 cohort B. Journal Of Clinical Oncology 2017, 35: 1088-1088. DOI: 10.1200/jco.2017.35.15_suppl.1088.Peer-Reviewed Original ResearchMetastatic triple-negative breast cancerPositive metastatic triple-negative breast cancerFirst-line therapyCombined positive scorePD-L1 combined positive scoreTreatment-related AEsPD-L1Cohort BStandard first-line treatmentEnd pointTriple-negative breast cancerECOG PS 0Antitumor activityManageable safety profilePrimary end pointSecondary end pointsFirst-line treatmentPhase 2 studySystemic anticancer therapyNew treatment optionsBest overall responseMedian DoRMedian PFSPFS ratesIntolerable toxicity