2022
Phase Ib study of pembrolizumab in combination with trastuzumab emtansine for metastatic HER2-positive breast cancer
Waks AG, Keenan TE, Li T, Tayob N, Wulf GM, Richardson ET, Attaya V, Anderson L, Mittendorf EA, Overmoyer B, Winer EP, Krop IE, Agudo J, Van Allen EM, Tolaney SM. Phase Ib study of pembrolizumab in combination with trastuzumab emtansine for metastatic HER2-positive breast cancer. Journal For ImmunoTherapy Of Cancer 2022, 10: e005119. PMID: 36252998, PMCID: PMC9577940, DOI: 10.1136/jitc-2022-005119.Peer-Reviewed Original ResearchConceptsObjective response rateProgression-free survivalMetastatic breast cancerAdverse eventsBreast cancerT-DM1Immune biomarkersTrastuzumab emtansineHER2-positive metastatic breast cancerMetastatic HER2-positive breast cancerGrade 3 adverse eventsMedian progression-free survivalTreatment-related adverse eventsHuman epidermal growth factor receptor 2Cell death ligand 1HER2-positive breast cancerEpidermal growth factor receptor 2Dose-finding cohortPhase 2 dosePhase Ib studyPhase Ib trialAnti-HER2 therapyDose-limiting toxicityGrowth factor receptor 2Immune checkpoint blockadeLocal Therapy Outcomes and Toxicity From the ATEMPT Trial (TBCRC 033): A Phase II Randomized Trial of Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab in Women With Stage I HER2-Positive Breast Cancer
Bellon JR, Tayob N, Yang DD, Tralins J, Dang CT, Isakoff SJ, DeMeo M, Burstein HJ, Partridge AH, Winer EP, Krop IE, Tolaney SM. Local Therapy Outcomes and Toxicity From the ATEMPT Trial (TBCRC 033): A Phase II Randomized Trial of Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab in Women With Stage I HER2-Positive Breast Cancer. International Journal Of Radiation Oncology • Biology • Physics 2022, 113: 117-124. PMID: 34990776, DOI: 10.1016/j.ijrobp.2021.12.173.Peer-Reviewed Original ResearchConceptsHER2-positive breast cancerBreast-conserving surgeryStage I HER2-positive breast cancerT-DM1 armBreast radiation therapyT-DM1Radiation therapySkin toxicityBreast cancerBCS patientsWBRT patientsInvasive disease-free survival eventsDisease-free survival eventsInvasive disease-free survivalHuman epidermal growth factor receptor 2Phase II Randomized TrialWhole breast radiation therapyEpidermal growth factor receptor 2Adjuvant T-DM1Adjuvant trastuzumab emtansineEfficacy of HER2RT-related toxicityWeeks of therapyAcute skin toxicityAnti-HER2 therapy
2021
Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2–Positive Early Breast Cancer: The Phase III KAITLIN Study
Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2–Positive Early Breast Cancer: The Phase III KAITLIN Study. Journal Of Clinical Oncology 2021, 40: 438-448. PMID: 34890214, PMCID: PMC8824393, DOI: 10.1200/jco.21.00896.Peer-Reviewed Original ResearchConceptsInvasive disease-free survivalOverall populationTrastuzumab emtansineHigh-risk human epidermal growth factor receptorHuman epidermal growth factor receptor 2End pointEpidermal growth factor receptor 2Early breast cancer treatmentHuman epidermal growth factor receptorAnthracycline-based chemotherapyCoprimary end pointsPrimary end pointDisease-free survivalSerious adverse eventsEarly breast cancerGlobal health statusGrowth factor receptor 2Treatment completion ratesStandard of careBreast cancer treatmentFactor receptor 2Epidermal growth factor receptorGrowth factor receptorEndocrine therapyAdverse eventsChemotherapy-related amenorrhea (CRA) after adjuvant ado-trastuzumab emtansine (T-DM1) compared to paclitaxel in combination with trastuzumab (TH) (TBCRC033: ATEMPT Trial)
Ruddy KJ, Zheng Y, Tayob N, Hu J, Dang CT, Yardley DA, Isakoff SJ, Valero VV, Faggen MG, Mulvey TM, Bose R, Sella T, Weckstein DJ, Wolff AC, Reeder-Hayes KE, Rugo HS, Ramaswamy B, Zuckerman DS, Hart LL, Gadi VK, Constantine M, Cheng KL, Briccetti FM, Schneider BP, Merrill Garrett A, Kelly Marcom P, Albain KS, DeFusco PA, Tung NM, Ardman BM, Nanda R, Jankowitz RC, Rimawi M, Abramson V, Pohlmann PR, Van Poznak C, Forero-Torres A, Liu MC, Rosenberg S, DeMeo MK, Burstein HJ, Winer EP, Krop IE, Partridge AH, Tolaney SM. Chemotherapy-related amenorrhea (CRA) after adjuvant ado-trastuzumab emtansine (T-DM1) compared to paclitaxel in combination with trastuzumab (TH) (TBCRC033: ATEMPT Trial). Breast Cancer Research And Treatment 2021, 189: 103-110. PMID: 34120223, DOI: 10.1007/s10549-021-06267-8.Peer-Reviewed Original ResearchConceptsChemotherapy-related amenorrheaEarly-stage breast cancerRisk of infertilityAdo-trastuzumab emtansineT-DM1Gonadotropin-releasing hormone agonistAdjuvant T-DM1T-DM1 3.6Amenorrhea ratesPermanent menopauseStandard HER2Chemotherapy regimensPrimary endpointProtocol therapyMedian ageOvarian toxicityPremature menopauseHormone agonistBreast cancerMenstrual dataMonthsAmenorrheaEmtansineMenopauseTrastuzumab
2017
T-DM1 — an important agent in the history of breast cancer management
Metzger-Filho O, Winer EP. T-DM1 — an important agent in the history of breast cancer management. Nature Reviews Clinical Oncology 2017, 14: 651-652. PMID: 28786416, DOI: 10.1038/nrclinonc.2017.123.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineBreast NeoplasmsCapecitabineHumansLapatinibMaytansineTrastuzumabConceptsT-DM1HER2-positive breast cancerOverall survival benefitFavorable safety profileBreast cancer managementRelevant therapeutic targetTH3RESA trialProlonged followSurvival benefitSafety profileBreast cancerCancer managementTherapeutic targetLater linesImportant agentsPatientsHER2FollowCancerDiseaseTrials
2014
Systemic Therapy for Patients With Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline
Giordano SH, Temin S, Kirshner JJ, Chandarlapaty S, Crews JR, Davidson NE, Esteva FJ, Gonzalez-Angulo AM, Krop I, Levinson J, Lin NU, Modi S, Patt DA, Perez EA, Perlmutter J, Ramakrishna N, Winer EP. Systemic Therapy for Patients With Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline. Journal Of Clinical Oncology 2014, 32: 2078-2099. PMID: 24799465, PMCID: PMC6076031, DOI: 10.1200/jco.2013.54.0948.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAnastrozoleAntibodies, Monoclonal, HumanizedAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsClinical Trials as TopicComorbidityDocetaxelDrug Administration ScheduleEvidence-Based MedicineFemaleHealth Status DisparitiesHealthcare DisparitiesHumansLapatinibLetrozoleMaytansineMolecular Targeted TherapyNitrilesQuinazolinesReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneSocieties, MedicalTaxoidsTrastuzumabTreatment OutcomeTriazolesUnited StatesConceptsAdvanced breast cancerHuman epidermal growth factor receptorSecond-line treatmentProgression-free survivalFirst-line treatmentBreast cancerPFS benefitT-DM1Epidermal growth factor receptorEndocrine therapyGrowth factor receptorSystemic therapyEstrogen receptor-positive/progesterone receptor-positive breast cancerAdvanced human epidermal growth factor receptorHER2-positive advanced breast cancerProgesterone receptor-positive breast cancerClinical Oncology Clinical Practice GuidelineClinical congestive heart failureStandard first-line therapyPositive advanced breast cancerLeft ventricular ejection fractionOncology Clinical Practice GuidelineReceptor-positive breast cancerThird-line settingFirst-line therapyTrastuzumab Emtansine: A Novel Antibody–Drug Conjugate for HER2-Positive Breast Cancer
Krop I, Winer EP. Trastuzumab Emtansine: A Novel Antibody–Drug Conjugate for HER2-Positive Breast Cancer. Clinical Cancer Research 2014, 20: 15-20. PMID: 24135146, DOI: 10.1158/1078-0432.ccr-13-0541.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerT-DM1Breast cancerAntibody-drug conjugatesAntibody-dependent cell-mediated cytotoxicityRecent phase III trialsHER2-positive breast cancerNovel antibody-drug conjugateCapecitabine/lapatinibFirst-line settingHepatic transaminase elevationsCombination of trastuzumabPhase II studyProgression-free survivalPhase III trialsInhibition of HER2Cell-mediated cytotoxicityFavorable toxicity profileHER2-positive tumor cellsMonoclonal antibody trastuzumabTransaminase elevationII studyIII trialsOverall survivalAdverse events
2012
A Phase II Study of Trastuzumab Emtansine in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer Who Were Previously Treated With Trastuzumab, Lapatinib, an Anthracycline, a Taxane, and Capecitabine
Krop IE, LoRusso P, Miller KD, Modi S, Yardley D, Rodriguez G, Guardino E, Lu M, Zheng M, Girish S, Amler L, Winer EP, Rugo HS. A Phase II Study of Trastuzumab Emtansine in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer Who Were Previously Treated With Trastuzumab, Lapatinib, an Anthracycline, a Taxane, and Capecitabine. Journal Of Clinical Oncology 2012, 30: 3234-3241. PMID: 22649126, DOI: 10.1200/jco.2011.40.5902.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAgedAnthracyclinesAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBreast NeoplasmsBridged-Ring CompoundsCapecitabineDeoxycytidineDisease-Free SurvivalFemaleFluorouracilHumansImmunotoxinsLapatinibMaleMaytansineMiddle AgedMolecular Targeted TherapyNeoplasm MetastasisQuinazolinesReceptor, ErbB-2TaxoidsTrastuzumabConceptsHER2-positive metastatic breast cancerHuman epidermal growth factor receptor 2Metastatic breast cancerProgression-free survivalOverall response rateMedian progression-free survivalPhase II studyT-DM1II studyTrastuzumab emtansineBreast cancerResponse rateSingle-arm phase II studyEpidermal growth factor receptor 2Human epidermal growth factor receptorClinical benefit rateHER2-directed therapiesMost adverse eventsGrowth factor receptor 2Single-agent activityHER2-positive tumorsMultiple chemotherapy agentsEffective new treatmentsFactor receptor 2Epidermal growth factor receptor
2011
Responses to subsequent anti-HER2 therapy after treatment with trastuzumab-DM1 in women with HER2-positive metastatic breast cancer
Olson EM, Lin NU, DiPiro PJ, Najita JS, Krop IE, Winer EP, Burstein HJ. Responses to subsequent anti-HER2 therapy after treatment with trastuzumab-DM1 in women with HER2-positive metastatic breast cancer. Annals Of Oncology 2011, 23: 93-97. PMID: 21531783, PMCID: PMC3276325, DOI: 10.1093/annonc/mdr061.Peer-Reviewed Original ResearchConceptsAnti-HER2 therapyMetastatic breast cancerHER2-positive MBC patientsT-DM1MBC patientsBreast cancerHER2-positive metastatic breast cancerSingle-agent T-DM1Positive metastatic breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Blinded radiology reviewAnti-HER2 agentsGrowth factor receptor 2Kaplan-Meier estimatesFurther clinical benefitFactor receptor 2Protocol therapyMedian durationFurther therapyPartial responseRadiology reviewClinical benefitSubsequent linesMetastatic therapy