2019
Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase II KEYNOTE-086 study
Adams S, Schmid P, Rugo HS, Winer EP, Loirat D, Awada A, Cescon DW, Iwata H, Campone M, Nanda R, Hui R, Curigliano G, Toppmeyer D, O’Shaughnessy J, Loi S, Paluch-Shimon S, Tan AR, Card D, Zhao J, Karantza V, Cortés J. Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase II KEYNOTE-086 study. Annals Of Oncology 2019, 30: 397-404. PMID: 30475950, DOI: 10.1093/annonc/mdy517.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerTriple-negative breast cancerDisease control ratePD-L1Positive populationPembrolizumab monotherapyMetastatic diseaseControl rateBreast cancerTreatment-related adverse eventsEnd pointManageable safety profileObjective response ratePrimary end pointSecondary end pointsProgression-free survivalSubset of patientsDurable antitumor activityDuration of responseLine of treatmentEligible patientsMedian OSMedian PFSAdverse eventsMedian duration
2017
A mouse-human phase I co-clinical trial of taselisib in combination with TDM1 in advanced HER2-positive breast cancer (MBC).
Metzger Filho O, Goel S, Barry W, Hamilton E, Tolaney S, Yardley D, Rees R, Demeo M, Mills C, Hafner M, Winer E, Zhao J, Krop I. A mouse-human phase I co-clinical trial of taselisib in combination with TDM1 in advanced HER2-positive breast cancer (MBC). Journal Of Clinical Oncology 2017, 35: 1030-1030. DOI: 10.1200/jco.2017.35.15_suppl.1030.Peer-Reviewed Original ResearchPhase Ib studyT-DM1Co-clinical trialsIb studyAdvanced HER2-positive breast cancerT-DM1-resistant cellsHER2-positive breast cancerPR/CRAcceptable safety profileAnti-HER2 therapyPI3K blockadePre-clinical experimentsConfirmed responsesMedian PFSPJP prophylaxisMedian durationMedian agePIK3CA H1047RPIK3CA statusSafety profilePneumocystis pneumoniaHER2 expressionClinical resultsMammary carcinomaBreast cancerPhase 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 0Phase 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
2016
Phase III Trial Evaluating Letrozole As First-Line Endocrine Therapy With or Without Bevacizumab for the Treatment of Postmenopausal Women With Hormone Receptor–Positive Advanced-Stage Breast Cancer: CALGB 40503 (Alliance)
Dickler MN, Barry WT, Cirrincione CT, Ellis MJ, Moynahan ME, Innocenti F, Hurria A, Rugo HS, Lake DE, Hahn O, Schneider BP, Tripathy D, Carey LA, Winer EP, Hudis CA. Phase III Trial Evaluating Letrozole As First-Line Endocrine Therapy With or Without Bevacizumab for the Treatment of Postmenopausal Women With Hormone Receptor–Positive Advanced-Stage Breast Cancer: CALGB 40503 (Alliance). Journal Of Clinical Oncology 2016, 34: 2602-2609. PMID: 27138575, PMCID: PMC5012690, DOI: 10.1200/jco.2015.66.1595.Peer-Reviewed Original ResearchConceptsProlong progression-free survivalHormone receptor-positive metastatic breast cancerMetastatic breast cancerAddition of bevacizumabMedian PFSMeasurable diseaseOverall survivalGrade 3Breast cancerAnti-vascular endothelial growth factor therapyBevacizumab prolongs progression-free survivalDe novo metastatic breast cancerEndothelial growth factor therapyNovo metastatic breast cancerRole of bevacizumabTrial of letrozoleMedian overall survivalTreatment-related toxicityDisease-free intervalPhase III trialsProgression-free survivalGrowth factor therapyStage breast cancerHazard of progressionLine endocrine therapy
2013
A phase II study of bevacizumab in combination with vinorelbine and trastuzumab in HER2-positive metastatic breast cancer
Lin NU, Seah DS, Gelman R, Desantis S, Mayer EL, Isakoff S, DiPiro P, Krop IE, Come SE, Weckstein D, Winer EP, Burstein HJ. A phase II study of bevacizumab in combination with vinorelbine and trastuzumab in HER2-positive metastatic breast cancer. Breast Cancer Research And Treatment 2013, 139: 403-410. PMID: 23645007, DOI: 10.1007/s10549-013-2551-9.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerGrade 3/4 non-hematologic toxicitiesHER2-positive metastatic breast cancerNon-hematologic toxicitiesTreatment-related toxicityBreast cancerCommon treatment-related toxicitiesFirst-line patientsProtocol-based therapySecond-line cohortSecond-line patientsSecond-line settingPhase II studyProportion of patientsCombination of vinorelbineCo-primary endpointsEligible patientsFebrile neutropeniaMedian PFSII studyMedian durationObjective responsePrior linesUnacceptable toxicityMedian age
2012
HALT MBC: HER2 suppression with the addition of lapatinib to trastuzumab in HER2-positive metastatic breast cancer (LPT112515).
Lin N, Danso M, David A, Muscato J, Rayson D, Houck W, Ellis C, DeSilvio M, Garofalo A, Nagarwala Y, Winer E. HALT MBC: HER2 suppression with the addition of lapatinib to trastuzumab in HER2-positive metastatic breast cancer (LPT112515). Journal Of Clinical Oncology 2012, 30: tps658-tps658. DOI: 10.1200/jco.2012.30.15_suppl.tps658.Peer-Reviewed Original ResearchHER2-positive metastatic BCSecond-line treatmentMetastatic BCOverall survivalHigher pathologic complete response rateHER2-positive metastatic breast cancerBreast cancer preclinical modelsPathologic complete response rateClinical benefit rateDual HER2 blockadeStable brain metastasesComplete response rateCombination of trastuzumabHormone receptor statusPhase III studyAddition of lapatinibKey eligibility criteriaMetastatic breast cancerLine of treatmentChemotherapy discontinuationHER2 blockadeITT populationMedian PFSStable diseaseBrain metastases
2011
OT1-02-02: HALT MBC: HER2 Suppression with the Addition of Lapatinib to Trastuzumab in HER2−Positive Metastatic Breast Cancer (LPT112515).
Lin N, Danso M, David A, Muscato J, Ellis C, DeSilvio M, Garofalo A, Nagarwala Y, Winer E. OT1-02-02: HALT MBC: HER2 Suppression with the Addition of Lapatinib to Trastuzumab in HER2−Positive Metastatic Breast Cancer (LPT112515). Cancer Research 2011, 71: ot1-02-02-ot1-02-02. DOI: 10.1158/0008-5472.sabcs11-ot1-02-02.Peer-Reviewed Original ResearchSecond-line treatmentAddition of lapatinibOverall survivalHigher pathological complete response rateBreast cancer preclinical modelsPathological complete response rateClinical benefit rateDual HER2 blockadeStable brain metastasesComplete response rateHormone receptor statusPhase III studyMetastatic breast cancerLine of treatmentAnti-tumor activityHER2 blockadeMedian PFSStable diseaseBrain metastasesEfficacy endpointMaintenance therapyPreoperative treatmentAdverse eventsHazard ratioIII studyP3-16-05: A Phase II Trial Expansion Cohort of the PARP Inhibitor Veliparib (ABT888) and Temozolomide in BRCA1/2 Associated Metastatic Breast Cancer.
Isakoff S, Overmoyer B, Tung N, Gelman R, Habin K, Qian J, Giranda V, Shepherd S, Garber J, Ellisen L, Winer E, Goss P. P3-16-05: A Phase II Trial Expansion Cohort of the PARP Inhibitor Veliparib (ABT888) and Temozolomide in BRCA1/2 Associated Metastatic Breast Cancer. Cancer Research 2011, 71: p3-16-05-p3-16-05. DOI: 10.1158/0008-5472.sabcs11-p3-16-05.Peer-Reviewed Original ResearchMetastatic breast cancerClinical benefit ratePrior platinum treatmentExpansion cohortResponse rateBenefit ratePlatinum treatmentPo bidPrior platinumMedian PFSAdditional patientsOriginal cohortBreast cancerCommon grade 3/4 toxicitiesSingle-arm phase II trialArm phase II trialBreast cancer xenograft modelPARP inhibitor veliparibPrior adjuvant chemotherapySafety of temozolomideGrade 3/4 toxicitiesPhase II studyFirst-line therapyPhase II trialOverall response rate