2022
The oral selective estrogen receptor degrader GDC-0810 (ARN-810) in postmenopausal women with hormone receptor-positive HER2-negative (HR + /HER2 −) advanced/metastatic breast cancer
Bardia A, Mayer I, Winer E, Linden H, Ma C, Parker B, Bellet M, Arteaga C, Cheeti S, Gates M, Chang C, Fredrickson J, Spoerke J, Moore H, Giltnane J, Friedman L, Chow Maneval E, Chan I, Jhaveri K. The oral selective estrogen receptor degrader GDC-0810 (ARN-810) in postmenopausal women with hormone receptor-positive HER2-negative (HR + /HER2 −) advanced/metastatic breast cancer. Breast Cancer Research And Treatment 2022, 197: 319-331. PMID: 36401732, PMCID: PMC9823088, DOI: 10.1007/s10549-022-06797-9.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerSelective estrogen receptor degraderDose escalationESR1 mutationsPostmenopausal womenBreast cancerEstrogen receptorCombination treatmentNon-complete response/non-progressive diseaseAdvanced/Metastatic Breast CancerOral selective estrogen receptor degraderPreliminary anti-tumor activityESR1 mutation statusPhase 2 dosePlasma ctDNA samplesCommon adverse eventsNon-progressive diseaseDose-limiting toxicityHormone-releasing hormoneSelective estrogen receptorAnti-tumor activityStable diseaseAdverse eventsPartial responseProgressive diseasePhase 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 blockade
2021
A Phase 1 Dose-Escalation Trial of Radiation Therapy and Concurrent Cisplatin for Stage II and III Triple-Negative Breast Cancer
Bellon JR, Chen YH, Rees R, Taghian AG, Wong JS, Punglia RS, Shiloh RY, Warren LEG, Krishnan MS, Phillips J, Pretz J, Jimenez R, Macausland S, Pashtan I, Andrews C, Isakoff SJ, Winer EP, Tolaney SM. A Phase 1 Dose-Escalation Trial of Radiation Therapy and Concurrent Cisplatin for Stage II and III Triple-Negative Breast Cancer. International Journal Of Radiation Oncology • Biology • Physics 2021, 111: 45-52. PMID: 33713742, DOI: 10.1016/j.ijrobp.2021.03.002.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerBreast-conserving therapyDose-limiting toxicityBCT cohortRadiation therapyConcurrent cisplatinMastectomy cohortBreast cancerEarly-stage triple-negative breast cancerThree-year disease-free survivalPhase 1 dose-escalation trialStage IILocal-regional recurrence ratePhase 2 doseAdjuvant radiation therapyDisease-free survivalDose-escalation trialPhase 1b trialDose of cisplatinHER2-positive tumorsEligible patientsUrinary infectionAdditional patientsDose escalationRecurrence rate
2020
Phase I dose-escalation trial of tucatinib in combination with trastuzumab in patients with HER2-positive breast cancer brain metastases
Filho O, Leone JP, Li T, Tan-Wasielewski Z, Trippa L, Barry WT, Younger J, Lawler E, Walker L, Freedman RA, Tolaney SM, Krop I, Winer EP, Lin NU. Phase I dose-escalation trial of tucatinib in combination with trastuzumab in patients with HER2-positive breast cancer brain metastases. Annals Of Oncology 2020, 31: 1231-1239. PMID: 32461105, DOI: 10.1016/j.annonc.2020.05.014.Peer-Reviewed Original ResearchConceptsClinical benefit rateHER2-positive brain metastasesAlanine aminotransferase elevationCohort ABrain metastasesCohort BAminotransferase elevationBreast cancerHER2-positive breast cancer brain metastasesPhase I dose-escalation trialMedian progression-free survivalBreast cancer brain metastasesCommon dose-limiting toxicityI dose-escalation trialHER2-positive breast cancerCombination of tucatinibSecondary end pointsCancer brain metastasesDose-escalation trialProgression-free survivalDose-limiting toxicityMetastatic breast cancerBrain radiationObjective responseIntracranial activity
2018
A phase Ib study of pictilisib (GDC-0941) in combination with paclitaxel, with and without bevacizumab or trastuzumab, and with letrozole in advanced breast cancer
Schöffski P, Cresta S, Mayer IA, Wildiers H, Damian S, Gendreau S, Rooney I, Morrissey KM, Spoerke JM, Ng VW, Singel SM, Winer E. A phase Ib study of pictilisib (GDC-0941) in combination with paclitaxel, with and without bevacizumab or trastuzumab, and with letrozole in advanced breast cancer. Breast Cancer Research 2018, 20: 109. PMID: 30185228, PMCID: PMC6125885, DOI: 10.1186/s13058-018-1015-x.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityPhase Ib studyMetastatic breast cancerAdverse eventsBreast cancerIb studyResultsSixty-nine patientsAntitumor activityManageable safety profileAdvanced breast cancerSerious adverse eventsPreliminary antitumor activityDrug-drug interactionsEvaluation of safetySecondary endpointsPartial responseComplete responseDose escalationRandomized studySafety profilePatientsBevacizumabTrastuzumabPictilisibLetrozole
2017
Kinetic-Pharmacodynamic Model of Chemotherapy-Induced Peripheral Neuropathy in Patients with Metastatic Breast Cancer Treated with Paclitaxel, Nab-Paclitaxel, or Ixabepilone: CALGB 40502 (Alliance)
Mehrotra S, Sharma MR, Gray E, Wu K, Barry WT, Hudis C, Winer EP, Lyss AP, Toppmeyer DL, Moreno-Aspitia A, Lad TE, Valasco M, Overmoyer B, Rugo H, Ratain MJ, Gobburu JV. Kinetic-Pharmacodynamic Model of Chemotherapy-Induced Peripheral Neuropathy in Patients with Metastatic Breast Cancer Treated with Paclitaxel, Nab-Paclitaxel, or Ixabepilone: CALGB 40502 (Alliance). The AAPS Journal 2017, 19: 1411-1423. PMID: 28620884, PMCID: PMC5711539, DOI: 10.1208/s12248-017-0101-9.Peer-Reviewed Original ResearchConceptsChemotherapy-induced peripheral neuropathyProportion of patientsMetastatic breast cancerKinetic-pharmacodynamic modelIndirect response modelNab-paclitaxelDose modificationPeripheral neuropathyBreast cancerDrug effectsRandomized phase III trialLinear drug effectFirst-line chemotherapyPhase III trialsTime pointsDose-limiting toxicityLater time pointsEarly time pointsCALGB 40502Neurotoxicity ScaleIII trialsFunctional assessmentChemotherapeutic agentsPatientsCancerA Phase Ib Study of Alpelisib (BYL719), a PI3Kα-Specific Inhibitor, with Letrozole in ER+/HER2− Metastatic Breast Cancer
Mayer IA, Abramson VG, Formisano L, Balko JM, Estrada MV, Sanders ME, Juric D, Solit D, Berger MF, Won HH, Li Y, Cantley LC, Winer E, Arteaga CL. A Phase Ib Study of Alpelisib (BYL719), a PI3Kα-Specific Inhibitor, with Letrozole in ER+/HER2− Metastatic Breast Cancer. Clinical Cancer Research 2017, 23: 26-34. PMID: 27126994, PMCID: PMC5085926, DOI: 10.1158/1078-0432.ccr-16-0134.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsAromatase InhibitorsBiomarkers, TumorBreast NeoplasmsCell Line, TumorDNA Mutational AnalysisFemaleHumansIn Situ Hybridization, FluorescenceLetrozoleMaximum Tolerated DoseMiddle AgedMutationNeoplasm MetastasisNeoplasm StagingNitrilesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsReceptor, ErbB-2Receptor, Fibroblast Growth Factor, Type 1Receptors, EstrogenThiazolesTreatment OutcomeTriazolesConceptsMaximum-tolerated doseBreast cancer cellsEndocrine therapyClinical benefitCommon drug-related adverse eventsDrug-related adverse eventsMutant breast cancer cellsBreast cancer refractoryPIK3CA mutation statusPIK3CA-mutated tumorsClinical benefit ratePhase Ib studyPI3K catalytic subunit p110αDose-limiting toxicityCancer cellsSelective oral inhibitorOverexpression of FGFR1Combination of letrozoleSynergistic antitumor activityCatalytic subunit p110αCancer refractoryFGFR1/2 amplificationMetastatic ERAdverse eventsObjective response
2014
Phase I/II study of pilaralisib (SAR245408) in combination with trastuzumab or trastuzumab plus paclitaxel in trastuzumab-refractory HER2-positive metastatic breast cancer
Tolaney S, Burris H, Gartner E, Mayer IA, Saura C, Maurer M, Ciruelos E, Garcia AA, Campana F, Wu B, Xu Y, Jiang J, Winer E, Krop I. Phase I/II study of pilaralisib (SAR245408) in combination with trastuzumab or trastuzumab plus paclitaxel in trastuzumab-refractory HER2-positive metastatic breast cancer. Breast Cancer Research And Treatment 2014, 149: 151-161. PMID: 25537644, DOI: 10.1007/s10549-014-3248-4.Peer-Reviewed Original ResearchConceptsHER2-positive metastatic breast cancerMetastatic breast cancerAdverse eventsBreast cancerArm 2Arm 1Phase I/II dose-escalation studyMetastatic HER2-positive breast cancerPhase I/II studyTreatment-related adverse eventsHER2-positive breast cancerTreatment-related gradeAcceptable safety profileDose-escalation studyDose-limiting toxicityDose-escalation designPan-class IEvaluable patientsPaclitaxel armPrior taxanePrior trastuzumabErythematous rashII studyPartial responsePeripheral neuropathyPolygenic inheritance of paclitaxel-induced sensory peripheral neuropathy driven by axon outgrowth gene sets in CALGB 40101 (Alliance)
Chhibber A, Mefford J, Stahl EA, Pendergrass SA, Baldwin RM, Owzar K, Li M, Winer EP, Hudis CA, Zembutsu H, Kubo M, Nakamura Y, McLeod HL, Ratain MJ, Shulman LN, Ritchie MD, Plenge RM, Witte JS, Kroetz DL. Polygenic inheritance of paclitaxel-induced sensory peripheral neuropathy driven by axon outgrowth gene sets in CALGB 40101 (Alliance). The Pharmacogenomics Journal 2014, 14: 336-342. PMID: 24513692, PMCID: PMC4111770, DOI: 10.1038/tpj.2014.2.Peer-Reviewed Original ResearchConceptsSensory peripheral neuropathyPaclitaxel-induced peripheral neuropathyPeripheral neuropathyCALGB 40101Common dose-limiting toxicityPhase III clinical trialsPaclitaxel-induced neuropathyDose-limiting toxicityAxon outgrowthPaclitaxel armAdjuvant therapyAdverse eventsSusceptible patientsRisk factorsClinical trialsBreast cancerNeuropathyPaclitaxel treatmentClinical decisionPatientsPatient informationMaximum gradeHeritable componentMost individualsTreatment
2013
A phase I study of lapatinib with whole brain radiotherapy in patients with Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer brain metastases
Lin NU, Freedman RA, Ramakrishna N, Younger J, Storniolo AM, Bellon JR, Come SE, Gelman RS, Harris GJ, Henderson MA, MacDonald SM, Mahadevan A, Eisenberg E, Ligibel JA, Mayer EL, Moy B, Eichler AF, Winer EP. A phase I study of lapatinib with whole brain radiotherapy in patients with Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer brain metastases. Breast Cancer Research And Treatment 2013, 142: 405-414. PMID: 24197661, DOI: 10.1007/s10549-013-2754-0.Peer-Reviewed Original ResearchConceptsWhole brain radiotherapyDose-limiting toxicityObjective response rateHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Growth factor receptor 2Positive breast cancerCentral nervous diseasesBrain metastasesFactor receptor 2Brain radiotherapyBreast cancerReceptor 2CNS objective response rateBreast cancer brain metastasesHigher objective response rateCareful safety monitoringCancer brain metastasesGrade 3 rashPre-defined criteriaEligible patientsEvaluable patientsLapatinib 1000Pulmonary emboliDose escalation
2012
Combination antiangiogenic therapy in advanced breast cancer: a phase 1 trial of vandetanib, a VEGFR inhibitor, and metronomic chemotherapy, with correlative platelet proteomics
Mayer EL, Isakoff SJ, Klement G, Downing SR, Chen WY, Hannagan K, Gelman R, Winer EP, Burstein HJ. Combination antiangiogenic therapy in advanced breast cancer: a phase 1 trial of vandetanib, a VEGFR inhibitor, and metronomic chemotherapy, with correlative platelet proteomics. Breast Cancer Research And Treatment 2012, 136: 169-178. PMID: 23001754, PMCID: PMC5472381, DOI: 10.1007/s10549-012-2256-5.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, MetronomicAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, PharmacologicalBlood PlateletsBreast NeoplasmsCombined Modality TherapyCyclophosphamideDrug-Related Side Effects and Adverse ReactionsFemaleGene Expression Regulation, NeoplasticHumansMethotrexateMiddle AgedNeoplasm StagingNeovascularization, PathologicPiperidinesPlatelet Factor 4ProteomicsQuinazolinesVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1ConceptsMetastatic breast cancerBreast cancerMetronomic chemotherapyAntiangiogenic therapyCombination antiangiogenic therapyDose-escalation cohortsPrior chemotherapy regimensResponse-evaluable patientsAdvanced breast cancerModest clinical activityDose-limiting toxicityPhase 1 studyPhase 1 trialVascular endothelial growth factorPlatelet factor 4Platelet-associated proteinsEndothelial growth factorEligible patientsLFT abnormalitiesMetronomic cyclophosphamideStable diseaseChemotherapy regimensPrimary endpointSecondary endpointsPartial responsePhase I, open-label study of olaparib plus cisplatin in patients with advanced solid tumors.
Balmaña J, Tung N, Isakoff S, Graña B, Ryan P, Rafi R, Tracy M, Winer E, Baselga J, Garber J. Phase I, open-label study of olaparib plus cisplatin in patients with advanced solid tumors. Journal Of Clinical Oncology 2012, 30: 1009-1009. DOI: 10.1200/jco.2012.30.15_suppl.1009.Peer-Reviewed Original ResearchAdvanced solid tumorsHematologic AEsEvaluable ptsMonotherapy phaseDose reductionSolid tumorsAntitumor activityOpen-label studyDose-limiting toxicityCisplatin-related toxicityDose-finding studyDrug-related deathsOral PARP inhibitorLong respondersOlaparib capsulesNeoadjuvant settingPrior regimensStable diseaseDurable responsesObjective responsePeritoneal cancerTherapy cyclesMedian numberBreast cancerTreatment cycles
2005
Prospective evaluation of concurrent paclitaxel and radiation therapy after adjuvant doxorubicin and cyclophosphamide chemotherapy for Stage II or III breast cancer
Burstein HJ, Bellon JR, Galper S, Lu HM, Kuter I, Taghian AG, Wong J, Gelman R, Bunnell CA, Parker LM, Garber JE, Winer EP, Harris JR, Powell SN. Prospective evaluation of concurrent paclitaxel and radiation therapy after adjuvant doxorubicin and cyclophosphamide chemotherapy for Stage II or III breast cancer. International Journal Of Radiation Oncology • Biology • Physics 2005, 64: 496-504. PMID: 16243442, DOI: 10.1016/j.ijrobp.2005.07.975.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantCyclophosphamideDoxorubicinDrug Administration ScheduleFeasibility StudiesFemaleHumansPaclitaxelProspective StudiesRadiation PneumonitisRadiation-Sensitizing AgentsRadiotherapy DosageRadiotherapy, AdjuvantConceptsRadiation therapyBreast cancerAdjuvant doxorubicinConcurrent paclitaxelWeekly paclitaxelAC chemotherapyConcurrent radiationConcurrent treatmentGrade 2 radiation pneumonitisStage IIEarly-stage breast cancerAdjuvant AC chemotherapyDefinitive breast surgeryOperable stage IIWeekly paclitaxel treatmentConcurrent radiation therapyDose-limiting toxicityProtocol-based treatmentAdjuvant chemotherapyPaclitaxel scheduleSteroid therapyCyclophosphamide chemotherapyRadiation pneumonitisPulmonary injuryRadiation dermatitis
1999
Vinorelbine as first-line chemotherapy for advanced breast cancer in women 60 years of age or older
Vogel C, O’Rourke M, Winer E, Hochster H, Chang A, Adamkiewicz B, White R, McGuirt C. Vinorelbine as first-line chemotherapy for advanced breast cancer in women 60 years of age or older. Annals Of Oncology 1999, 10: 397-402. PMID: 10370781, DOI: 10.1023/a:1008364222793.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAgingAntineoplastic Agents, PhytogenicBreast NeoplasmsDisease-Free SurvivalDose-Response Relationship, DrugDrug Administration ScheduleFemaleFollow-Up StudiesHumansInfusions, IntravenousMiddle AgedProspective StudiesSeverity of Illness IndexTreatment OutcomeVinblastineVinorelbineConceptsAdvanced breast cancerDose-limiting toxicityBreast cancerSide effectsNonhematologic toxicityElderly patientsMeasurable advanced breast cancerMajor dose-limiting toxicityActivity of vinorelbineMedian dose intensityFirst-line chemotherapyObjective response rateFirst-line therapyPhase II trialSubjective side effectsInjection site reactionsWomen 60 yearsGastrointestinal side effectsGeneralized painIntravenous vinorelbinePrior chemotherapyAbdominal painChest painII trialCytotoxic chemotherapyInability to escalate vinorelbine dose intensity using a daily × 3 schedule with and without filgrastim in patients with metastatic breast cancer
Havlin K, Ramirez M, Legler C, Harris L, Matulonis U, Hohneker J, Hayes D, Winer E. Inability to escalate vinorelbine dose intensity using a daily × 3 schedule with and without filgrastim in patients with metastatic breast cancer. Cancer Chemotherapy And Pharmacology 1999, 43: 68-72. PMID: 9923543, DOI: 10.1007/s002800050864.Peer-Reviewed Original ResearchConceptsDana-Farber Cancer InstituteDuke University Medical CenterDose-limiting toxicityGrowth factor supportGrade III neurotoxicityMetastatic breast cancerFebrile neutropeniaBreast cancerFactor supportNonhematologic toxicityStarting doseDose intensityDay 4Stage IV breast cancerMajor dose-limiting toxicityAddition of filgrastimAlternative treatment regimenGrade III stomatitisGrade III vomitingGrade IV mucositisGrade IV thrombocytopeniaGreater nonhematologic toxicityPerformance status 0Prior chemotherapy regimensSemisynthetic vinca alkaloid
1992
High-Dose Oral Tamoxifen, a Potential Multidrug-Resistance-Reversal Agent: Phase I Trial in Combination With Vinblastine
Trump DL, Smith DC, Ellis PG, Rogers MP, Schold SC, Winer EP, Panella TJ, Jordan VC, Fine RL. High-Dose Oral Tamoxifen, a Potential Multidrug-Resistance-Reversal Agent: Phase I Trial in Combination With Vinblastine. Journal Of The National Cancer Institute 1992, 84: 1811-1816. PMID: 1359155, DOI: 10.1093/jnci/84.23.1811.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAntineoplastic Combined Chemotherapy ProtocolsATP Binding Cassette Transporter, Subfamily B, Member 1Drug Administration ScheduleDrug ResistanceFemaleHumansInfusions, IntravenousMaleMembrane GlycoproteinsMiddle AgedNeoplasm ProteinsNeoplasmsTamoxifenVinblastineConceptsLoading doseN-desmethyltamoxifenOral tamoxifenContinuous infusionPlasma concentrationsHigh-dose oral tamoxifenDose-limiting toxic effectPhase I clinical trialAdvanced epithelial tumorsHigh-dose tamoxifenTriphenylethylene antiestrogen tamoxifenPhase II trialDose-limiting toxicityPhase I trialDoses of tamoxifenStart of treatmentP-glycoprotein functionToxicity of vinblastineAnti-neoplastic agentsToxic effectsMetabolite N-desmethyltamoxifenIntracellular concentrationAsymptomatic prolongationStarting doseII trialModulation of O6-alkylguanine-DNA alkyltransferase-mediated carmustine resistance using streptozotocin: a phase I trial.
Panella TJ, Smith DC, Schold SC, Rogers MP, Winer EP, Fine RL, Crawford J, Herndon JE, Trump DL. Modulation of O6-alkylguanine-DNA alkyltransferase-mediated carmustine resistance using streptozotocin: a phase I trial. Cancer Research 1992, 52: 2456-9. PMID: 1533174.Peer-Reviewed Original ResearchConceptsFmol/M2/dayDose-limiting toxicityPhase I trialDose of BCNUSerum alkaline phosphataseBCNU doseSTZ doseStarting dosePartial responseSerum creatinineThird doseDose escalationI trialMild elevationDay 3BCNU resistanceNitrosourea resistanceSTZBCNU cytotoxicityBCNUDoseAdditional studiesO6-alkylguanine-DNA alkyltransferaseAlkaline phosphatase