2020
A Randomized Placebo Controlled Phase II Trial Evaluating Exemestane with or without Enzalutamide in Patients with Hormone Receptor–Positive Breast Cancer
Krop I, Abramson V, Colleoni M, Traina T, Holmes F, Garcia-Estevez L, Hart L, Awada A, Zamagni C, Morris PG, Schwartzberg L, Chan S, Gucalp A, Biganzoli L, Steinberg J, Sica L, Trudeau M, Markova D, Tarazi J, Zhu Z, O'Brien T, Kelly C, Winer E, Yardley D. A Randomized Placebo Controlled Phase II Trial Evaluating Exemestane with or without Enzalutamide in Patients with Hormone Receptor–Positive Breast Cancer. Clinical Cancer Research 2020, 26: 6149-6157. PMID: 32988969, DOI: 10.1158/1078-0432.ccr-20-1693.Peer-Reviewed Original ResearchConceptsProgression-free survivalHormone receptor-positive breast cancerReceptor-positive breast cancerPhase II trialEndocrine therapyBreast cancerII trialAR mRNACohort 1Higher AR mRNA levelsLower ESR1 mRNA levelsET-naïve patientsGrade adverse eventsPrior endocrine therapyMetastatic breast cancerAndrogen receptor inhibitorMRNA levelsAR mRNA levelsESR1 mRNA levelsEnzalutamide armITT populationTreat populationAdvanced diseasePrimary endpointAdverse eventsIntracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial
Lin NU, Borges V, Anders C, Murthy RK, Paplomata E, Hamilton E, Hurvitz S, Loi S, Okines A, Abramson V, Bedard PL, Oliveira M, Mueller V, Zelnak A, DiGiovanna MP, Bachelot T, Chien AJ, O’Regan R, Wardley A, Conlin A, Cameron D, Carey L, Curigliano G, Gelmon K, Loibl S, Mayor J, McGoldrick S, An X, Winer EP. Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial. Journal Of Clinical Oncology 2020, 38: 2610-2619. PMID: 32468955, PMCID: PMC7403000, DOI: 10.1200/jco.20.00775.Peer-Reviewed Original ResearchConceptsHER2-positive breast cancerBrain metastasesProgression-free survivalRisk of deathBreast cancerOverall survivalControl armCNS-PFSIntracranial efficacyIntracranial progressionBaseline brain magnetic resonance imagingHuman epidermal growth factor receptor 2Intracranial objective response rateEpidermal growth factor receptor 2Brain magnetic resonance imagingMedian CNS-PFSRECIST 1.1 criteriaMedian overall survivalObjective response rateGrowth factor receptor 2Positive breast cancerFactor receptor 2Magnetic resonance imagingHER2CLIMB trialImproved antitumor activity
2019
Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer
Murthy RK, Loi S, Okines A, Paplomata E, Hamilton E, Hurvitz SA, Lin NU, Borges V, Abramson V, Anders C, Bedard PL, Oliveira M, Jakobsen E, Bachelot T, Shachar SS, Müller V, Braga S, Duhoux FP, Greil R, Cameron D, Carey LA, Curigliano G, Gelmon K, Hortobagyi G, Krop I, Loibl S, Pegram M, Slamon D, Palanca-Wessels MC, Walker L, Feng W, Winer EP. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. New England Journal Of Medicine 2019, 382: 597-609. PMID: 31825569, DOI: 10.1056/nejmoa1914609.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsBrain NeoplasmsBreast NeoplasmsCapecitabineConsolidation ChemotherapyDiarrheaDouble-Blind MethodFemaleHumansKaplan-Meier EstimateMiddle AgedOxazolesProgression-Free SurvivalProtein-Tyrosine KinasesPyridinesQuinazolinesReceptor, ErbB-2TrastuzumabConceptsHER2-positive metastatic breast cancerProgression-free survivalPlacebo-combination groupMetastatic breast cancerElevated aminotransferase levelsBrain metastasesBreast cancerOverall survivalAminotransferase levelsMedian progression-free survivalPalmar-plantar erythrodysesthesia syndromeBetter progression-free survivalPositive metastatic breast cancerHuman epidermal growth factor receptor 2End pointEpidermal growth factor receptor 2Common adverse eventsMedian overall survivalObjective response ratePrimary end pointSecondary end pointsGrowth factor receptor 2Overall survival outcomesRisk of diarrheaFactor receptor 2Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial
Schmid P, Rugo HS, Adams S, Schneeweiss A, Barrios CH, Iwata H, Diéras V, Henschel V, Molinero L, Chui SY, Maiya V, Husain A, Winer EP, Loi S, Emens LA, Investigators I. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet Oncology 2019, 21: 44-59. PMID: 31786121, DOI: 10.1016/s1470-2045(19)30689-8.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAlbuminsAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorDouble-Blind MethodFemaleFollow-Up StudiesHumansMiddle AgedNeoplasm InvasivenessNeoplasm MetastasisPaclitaxelPrognosisReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneSurvival RateTriple Negative Breast NeoplasmsYoung AdultConceptsMetastatic triple-negative breast cancerInterim overall survival analysisTriple-negative breast cancerOverall survival analysisTreatment-related deathsMedian overall survivalNab-paclitaxelPhase 3 trialOverall survivalTreat populationBreast cancerSurvival analysisAtezolizumab groupPlacebo groupInterim analysisTreatment groupsEastern Cooperative Oncology Group performance statusDay 1Interactive voice-web response systemInvestigator-assessed progression-free survivalMeaningful overall survival benefitNew treatment-related deathsProgression-free survival resultsSolid Tumors version 1.1Tumor-infiltrating immune cells
2018
Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer
Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Petrakova K, Blackwell KL, Winer EP, Janni W, Verma S, Conte P, Arteaga CL, Cameron DA, Mondal S, Su F, Miller M, Elmeliegy M, Germa C, O’Shaughnessy J. Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Annals Of Oncology 2018, 29: 1541-1547. PMID: 29718092, DOI: 10.1093/annonc/mdy155.Peer-Reviewed Original ResearchMeSH KeywordsAgedAminopyridinesAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsDouble-Blind MethodFemaleFollow-Up StudiesHumansLetrozoleLiver NeoplasmsLung NeoplasmsLymphatic MetastasisNeoplasm Recurrence, LocalPrognosisPurinesReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneSurvival RateConceptsProgression-free survivalFirst-line ribociclibOverall response rateMONALEESA-2 studySecondary end pointsAdvanced breast cancerBreast cancerEnd pointOverall survivalHER2-negative advanced breast cancerKey secondary end pointMedian progression-free survivalHuman epidermal growth factor receptorExploratory biomarker analysisExploratory end pointsImproved efficacy outcomesManageable toxicity profilePrimary end pointSecond interim analysisMetastatic breast cancerPhase III trialsESR1 mRNA levelsEpidermal growth factor receptorTP53 mutation statusBiomarker analysis
2016
TransCONFIRM: Identification of a Genetic Signature of Response to Fulvestrant in Advanced Hormone Receptor–Positive Breast Cancer
Jeselsohn R, Barry WT, Migliaccio I, Biagioni C, Zhao J, De Tribolet-Hardy J, Guarducci C, Bonechi M, Laing N, Winer EP, Brown M, Di Leo A, Malorni L. TransCONFIRM: Identification of a Genetic Signature of Response to Fulvestrant in Advanced Hormone Receptor–Positive Breast Cancer. Clinical Cancer Research 2016, 22: 5755-5764. PMID: 27185372, PMCID: PMC5124409, DOI: 10.1158/1078-0432.ccr-16-0148.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, HormonalBreast NeoplasmsDisease-Free SurvivalDouble-Blind MethodEpidermal Growth FactorEstradiolFemaleFulvestrantGene Expression ProfilingHepatocyte Nuclear Factor 3-alphaHumansMiddle AgedPostmenopauseReceptors, EstrogenSignal TransductionTranscription Factor AP-2TranscriptomeConceptsProgression-free survivalBreast cancerPredictive biomarkersCONFIRM studyMetastatic estrogen receptor-positive breast cancerEstrogen receptor-positive breast cancerReceptor-positive breast cancerGene signatureBiologic pathwaysAdvanced breast cancerMetastatic breast cancerMultivariate Cox modelPotential new therapeutic targetEstrogen receptor antagonistNew therapeutic targetsNegative predictive valuePrimary tumor samplesNovel gene signatureMetastatic ERPrimary ERReceptor antagonistFulvestrant treatmentDecreased responseCox modelER levelsRibociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer
Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Blackwell KL, André F, Winer EP, Janni W, Verma S, Conte P, Arteaga CL, Cameron DA, Petrakova K, Hart LL, Villanueva C, Chan A, Jakobsen E, Nusch A, Burdaeva O, Grischke EM, Alba E, Wist E, Marschner N, Favret AM, Yardley D, Bachelot T, Tseng LM, Blau S, Xuan F, Souami F, Miller M, Germa C, Hirawat S, O'Shaughnessy J. Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer. New England Journal Of Medicine 2016, 375: 1738-1748. PMID: 27717303, DOI: 10.1056/nejmoa1609709.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAminopyridinesAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsDisease-Free SurvivalDouble-Blind MethodDrug Administration ScheduleFemaleHumansKaplan-Meier EstimateLetrozoleMiddle AgedNeoplasm StagingNitrilesPurinesReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneTriazolesConceptsAdvanced breast cancerProgression-free survivalHuman epidermal growth factor receptor 2Overall response rateRibociclib groupBreast cancerPlacebo groupAdverse eventsInvestigator-assessed progression-free survivalHER2-negative advanced breast cancerResponse rateProgression-free survival ratesEnd pointEpidermal growth factor receptor 2Hormone receptorsCDK4/6 inhibitor ribociclibCommon grade 3Initial systemic treatmentPrevious systemic therapyPrimary end pointSecondary end pointsFirst-line treatmentPhase 3 trialRate of discontinuationGrowth factor receptor 2Extending Aromatase-Inhibitor Adjuvant Therapy to 10 Years
Goss PE, Ingle JN, Pritchard KI, Robert NJ, Muss H, Gralow J, Gelmon K, Whelan T, Strasser-Weippl K, Rubin S, Sturtz K, Wolff AC, Winer E, Hudis C, Stopeck A, Beck JT, Kaur JS, Whelan K, Tu D, Parulekar WR. Extending Aromatase-Inhibitor Adjuvant Therapy to 10 Years. New England Journal Of Medicine 2016, 375: 209-219. PMID: 27264120, PMCID: PMC5024713, DOI: 10.1056/nejmoa1604700.Peer-Reviewed Original ResearchConceptsContralateral breast cancerDisease-free survivalAromatase inhibitorsBreast cancerOverall survivalDisease-free survival ratesPositive early breast cancerAdjuvant aromatase inhibitorsNew-onset osteoporosisPlacebo-controlled trialPrimary end pointEarly breast cancerAnnual incidence rateTreatment of choiceBreast cancer recurrenceExtension of treatmentQuality of lifeBone painLetrozole groupAdjuvant therapyPlacebo groupPostmenopausal womenDisease recurrenceIncidence rateLower incidencePictilisib for oestrogen receptor-positive, aromatase inhibitor-resistant, advanced or metastatic breast cancer (FERGI): a randomised, double-blind, placebo-controlled, phase 2 trial
Krop IE, Mayer IA, Ganju V, Dickler M, Johnston S, Morales S, Yardley DA, Melichar B, Forero-Torres A, Lee SC, de Boer R, Petrakova K, Vallentin S, Perez EA, Piccart M, Ellis M, Winer E, Gendreau S, Derynck M, Lackner M, Levy G, Qiu J, He J, Schmid P. Pictilisib for oestrogen receptor-positive, aromatase inhibitor-resistant, advanced or metastatic breast cancer (FERGI): a randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet Oncology 2016, 17: 811-821. PMID: 27155741, PMCID: PMC5524539, DOI: 10.1016/s1470-2045(16)00106-6.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorBreast NeoplasmsDouble-Blind MethodDrug Resistance, NeoplasmEstradiolEstrogen Receptor AntagonistsFemaleFollow-Up StudiesFulvestrantHumansMiddle AgedNeoplasm Recurrence, LocalNeoplasm StagingPrognosisReceptor, ErbB-2Receptors, EstrogenSalvage TherapySurvival RateConceptsProgression-free survivalSerious adverse eventsTreatment-related serious adverse eventsWorse adverse eventsPlacebo groupAdverse eventsNon-measurable diseaseAromatase inhibitor treatmentPIK3CA mutationsBreast cancerDay 1Grade 3Inhibitor treatmentDay 15Cycle 1Median progression-free survivalHER2-negative breast cancerEndocrine-resistant breast cancerPIK3CA-mutated tumorsPhase 2 studyPhase 2 trialMetastatic breast cancerWeeks of treatmentAromatase inhibitor resistanceF Hoffmann-La Roche
2014
Endocrine Therapy With or Without Inhibition of Epidermal Growth Factor Receptor and Human Epidermal Growth Factor Receptor 2: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Fulvestrant With or Without Lapatinib for Postmenopausal Women With Hormone Receptor–Positive Advanced Breast Cancer—CALGB 40302 (Alliance)
Burstein HJ, Cirrincione CT, Barry WT, Chew HK, Tolaney SM, Lake DE, Ma C, Blackwell KL, Winer EP, Hudis CA. Endocrine Therapy With or Without Inhibition of Epidermal Growth Factor Receptor and Human Epidermal Growth Factor Receptor 2: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Fulvestrant With or Without Lapatinib for Postmenopausal Women With Hormone Receptor–Positive Advanced Breast Cancer—CALGB 40302 (Alliance). Journal Of Clinical Oncology 2014, 32: 3959-3966. PMID: 25348000, PMCID: PMC4251959, DOI: 10.1200/jco.2014.56.7941.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalDouble-Blind MethodEstradiolFemaleFulvestrantHormonesHumansLapatinibMiddle AgedPostmenopauseProportional Hazards ModelsQuinazolinesReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneTreatment OutcomeConceptsMedian progression-free survivalProgression-free survivalOverall survivalBreast cancerHormone receptor-positive advanced breast cancerHormone receptor-positive metastatic breast cancerAdvanced ER-positive breast cancerHuman epidermal growth factor receptor 2 (HER2) statusLonger median progression-free survivalEpidermal growth factor receptor 2 statusProgesterone receptor-positive tumorsHuman epidermal growth factor receptor 2ER-positive breast cancerEpidermal growth factor receptor 2Advanced breast cancerPhase III trialsGrowth factor receptor 2Metastatic breast cancerReceptor-positive tumorsHER2-positive tumorsAromatase inhibitor treatmentFactor receptor 2Epidermal growth factor receptorDifferential treatment effectsGrowth factor receptor
2010
Augmentation of venlafaxine and selective serotonin reuptake inhibitors with zolpidem improves sleep and quality of life in breast cancer patients with hot flashes
Joffe H, Partridge A, Giobbie-Hurder A, Li X, Habin K, Goss P, Winer E, Garber J. Augmentation of venlafaxine and selective serotonin reuptake inhibitors with zolpidem improves sleep and quality of life in breast cancer patients with hot flashes. Menopause The Journal Of The North American Menopause Society 2010, 17: 908-916. PMID: 20581724, DOI: 10.1097/gme.0b013e3181dbee1b.Peer-Reviewed Original ResearchMeSH KeywordsAdultBreast NeoplasmsChemotherapy, AdjuvantCyclohexanolsDouble-Blind MethodDrug Therapy, CombinationFemaleHot FlashesHumansHypnotics and SedativesMiddle AgedPlacebosPyridinesQuality of LifeSelective Serotonin Reuptake InhibitorsSleep Disorders, IntrinsicVenlafaxine HydrochlorideZolpidemConceptsSerotonin-norepinephrine reuptake inhibitorsSelective serotonin reuptake inhibitorsQuality of lifeSSRIs/serotonin-norepinephrine reuptake inhibitorsSerotonin reuptake inhibitorsBreast cancer survivorsHot flashesReuptake inhibitorsCancer survivorsHypnotic agentsSSRI/SNRI therapySSRI/SNRI usersNighttime hot flashesAdjuvant endocrine therapyAssociated sleep disturbancesBreast cancer patientsProportion of respondersSubjective sleep qualitySNRI therapySNRI usersBlinded treatmentEndocrine therapyPlacebo augmentationVenlafaxine XRNocturnal awakenings
2003
Phase II, randomized, double-blind study of two dose levels of arzoxifene in patients with locally advanced or metastatic breast cancer.
Buzdar A, O’Shaughnessy J, Booser DJ, Pippen JE, Jones SE, Munster PN, Peterson P, Melemed AS, Winer E, Hudis C. Phase II, randomized, double-blind study of two dose levels of arzoxifene in patients with locally advanced or metastatic breast cancer. Journal Of Clinical Oncology 2003, 21: 1007-14. PMID: 12637464, DOI: 10.1200/jco.2003.06.108.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Agents, HormonalBiomarkers, TumorBreast NeoplasmsDose-Response Relationship, DrugDouble-Blind MethodDrug Administration ScheduleDrug Resistance, NeoplasmEndometriumEstrogen Receptor ModulatorsFemaleHumansMiddle AgedPatient SelectionPiperidinesReceptors, EstrogenSurvival AnalysisTamoxifenThiophenesTreatment OutcomeConceptsMetastatic breast cancerClinical benefit rateBreast cancerTamoxifen refractoryTR patientsResponse rateDose levelsEnd pointSelective estrogen receptor modulatorsPhase II studyPrimary end pointSecondary end pointsTumor response rateDouble-blind studyEstrogen receptor statusMetastatic disease sitesEstrogen receptor modulatorsTreatment of TSSimilar TTPTamoxifen therapyII studyDaily doseLonger TTPReceptor statusDose-dependent toxicity