2024
ETHAN: A phase II study comparing different endocrine therapies for male breast cancer.
Leone J, Ruddy K, Rashid N, Giordano S, Gupta G, Hilsenbeck S, Gucalp A, Walsh E, Sukumar J, Makhlin I, Ortiz-Perez T, Spanheimer P, Calhoun B, Wolff A, Krop I, Thompson A. ETHAN: A phase II study comparing different endocrine therapies for male breast cancer. Journal Of Clinical Oncology 2024, 42: tps632-tps632. DOI: 10.1200/jco.2024.42.16_suppl.tps632.Peer-Reviewed Original ResearchResidual cancer burdenMale breast cancerPreoperative endocrine prognostic indexTranslational Breast Cancer Research ConsortiumBreast cancerEndocrine therapyKi-67Patient-reported outcomesNeoadjuvant phaseArm BAromatase inhibitorsHuman epidermal growth factor receptor 2 (HER2)-negative breast cancerOutcome of endocrine therapyResidual cancer burden indexWindow phaseCyclin-dependent kinase 4/6Ki-67 reductionHormone receptor-positivePhase II studyInflammatory breast cancerLack of clinical trialsPhase II trialHR+/HER2- breast cancerAnti-cancer therapyStandard of careTucatinib-trastuzumab-capecitabine for treatment of leptomeningeal metastasis in HER2+ breast cancer: TBCRC049 phase 2 study results.
O'Brien B, Murthy R, Berry D, Singareeka Raghavendra A, Gule-Monroe M, Johnson J, Schwartz-Gomez J, Topletz-Erickson A, Lobbous M, Melisko M, Morikawa A, Ferguson S, de Groot J, Krop I, Valero V, Rimawi M, Wolff A, Tripathy D, Lin N, Stringer-Reasor E. Tucatinib-trastuzumab-capecitabine for treatment of leptomeningeal metastasis in HER2+ breast cancer: TBCRC049 phase 2 study results. Journal Of Clinical Oncology 2024, 42: 2018-2018. DOI: 10.1200/jco.2024.42.16_suppl.2018.Peer-Reviewed Original ResearchHER2+ breast cancerLeptomeningeal metastasesPatient-reported outcomesBreast cancerObjective responseClinical examCSF cytologyEvidence of clinically meaningful benefitHER2-targeted tyrosine kinase inhibitorsMedian time to CNS progressionMetastatic HER2+ breast cancerKarnofsky performance status >Treatment of leptomeningeal metastasesAbnormal CSF cytologyPerformance status >Targeted neurological deficitsMDASI-BTPhase 2 studyTyrosine kinase inhibitorsClinically meaningful benefitPre-specified timepointsPreliminary efficacy dataCNS progressionMedian OSCNS metastasesTrastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): patient-reported outcomes from a randomised, open-label, multicentre, phase 3 trial
Fehm T, Cottone F, Dunton K, André F, Krop I, Park Y, De Laurentiis M, Miyoshi Y, Armstrong A, Borrego M, Yerushalmi R, Duhoux F, Takano T, Lu W, Egorov A, Kim S. Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): patient-reported outcomes from a randomised, open-label, multicentre, phase 3 trial. The Lancet Oncology 2024, 25: 614-625. PMID: 38697155, DOI: 10.1016/s1470-2045(24)00128-1.Peer-Reviewed Original ResearchConceptsTreatment of physician's choiceMetastatic breast cancerTreatment of physician's choice groupPatient-reported outcomesPhysician's choice groupTrastuzumab deruxtecan groupTrastuzumab deruxtecanPhase 3 trialHER2-positiveBreast cancerGlobal health statusPhysician's choiceEORTC QLQ-C30 global health statusPatient-reported outcome variablesOpen-labelQLQ-C30 global health statusTrastuzumab emtansineDefinitive deteriorationMedian time to definitive deteriorationHER2-positive metastatic breast cancerEastern Cooperative Oncology Group performance statusTreatment durationBlinded independent central reviewQuality of lifeProgression-free survival
2023
186O Patient-reported outcomes (PROs) from DESTINY-Breast02, a randomized phase III study of trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice (TPC) in patients (pts) with HER2–positive (HER2+) metastatic breast cancer (mBC)
Fehm T, Cottone F, Dunton K, André F, Krop I, Park Y, De Laurentiis M, Miyoshi Y, Armstrong A, Borrego M, Yerushalmi R, Duhoux F, Takano T, Lu W, Livings C, Egorov A, Kim S. 186O Patient-reported outcomes (PROs) from DESTINY-Breast02, a randomized phase III study of trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice (TPC) in patients (pts) with HER2–positive (HER2+) metastatic breast cancer (mBC). ESMO Open 2023, 8: 101375. DOI: 10.1016/j.esmoop.2023.101375.Peer-Reviewed Original Research
2022
Treatment discontinuation, patient-reported toxicities and quality-of-life by age following trastuzumab emtansine or paclitaxel/trastuzumab (ATEMPT)
Sella T, Zheng Y, Tayob N, Ruddy K, Freedman R, Dang C, Yardley D, Isakoff S, Valero V, DeMeo M, Burstein H, Winer E, Wolff A, Krop I, Partridge A, Tolaney S. Treatment discontinuation, patient-reported toxicities and quality-of-life by age following trastuzumab emtansine or paclitaxel/trastuzumab (ATEMPT). Npj Breast Cancer 2022, 8: 127. PMID: 36450763, PMCID: PMC9712612, DOI: 10.1038/s41523-022-00495-x.Peer-Reviewed Original ResearchHER2-positive breast cancerPatient-reported toxicityPatient-reported outcomesT-DM1Treatment discontinuationTrastuzumab emtansineBreast cancerStage I HER2-positive breast cancerAdjuvant trastuzumab emtansineExcellent disease outcomesLess activity impairmentPaclitaxel/trastuzumabSocial/familyPositive breast cancerSuperior QoLOlder patientsTreatment toleranceTreatment armsTreatment regimensEligible participantsGlobal QoLTherapy optionsActivity impairmentMultivariable modelDisease outcomePhase 2 trial of tucatinib plus trastuzumab deruxtecan in patients with HER2+ locally advanced or metastatic breast cancer with and without brain metastases (HER2CLIMB-04, trial in progress).
Krop I, Carey L, Ramos J, Chen Y, Hamilton E. Phase 2 trial of tucatinib plus trastuzumab deruxtecan in patients with HER2+ locally advanced or metastatic breast cancer with and without brain metastases (HER2CLIMB-04, trial in progress). Journal Of Clinical Oncology 2022, 40: tps1111-tps1111. DOI: 10.1200/jco.2022.40.16_suppl.tps1111.Peer-Reviewed Original ResearchHuman epidermal growth factor receptor 2Metastatic breast cancerDisease control rateProgression-free survivalDuration of responseBrain metastasesAntibody-drug conjugatesRECIST 1.1Trastuzumab deruxtecanInvestigator assessmentBreast cancerSmall molecule tyrosine kinase inhibitorsTopoisomerase I inhibitor payloadEpidermal growth factor receptor 2Monoclonal antibodiesBreast cancer xenograft modelActive brain metastasesResponse-evaluable patientsManageable safety profileObjective response ratePhase 2 studyPhase 2 trialGrowth factor receptor 2Limited treatment optionsPatient-reported outcomes
2021
Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT): A Randomized Clinical Trial
Tolaney SM, Tayob N, Dang C, Yardley DA, Isakoff SJ, Valero V, Faggen M, Mulvey T, Bose R, Hu J, Weckstein D, Wolff AC, Reeder-Hayes K, Rugo HS, Ramaswamy B, Zuckerman D, Hart L, Gadi VK, Constantine M, Cheng K, Briccetti F, Schneider B, Garrett AM, Marcom K, Albain K, DeFusco P, Tung N, Ardman B, Nanda R, Jankowitz RC, Rimawi M, Abramson V, Pohlmann PR, Van Poznak C, Forero-Torres A, Liu M, Ruddy K, Zheng Y, Rosenberg SM, Gelber RD, Trippa L, Barry W, DeMeo M, Burstein H, Partridge A, Winer EP, Krop I. Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT): A Randomized Clinical Trial. Journal Of Clinical Oncology 2021, 39: 2375-2385. PMID: 34077270, DOI: 10.1200/jco.20.03398.Peer-Reviewed Original ResearchConceptsInvasive disease-free survivalT-DM1Breast cancerStage IStage I HER2-positive breast cancerHER2-positive breast cancerHuman epidermal growth factor receptorAdjuvant T-DM1Co-primary objectivesDisease-free survivalPatient-reported outcomesEpidermal growth factor receptorGrowth factor receptorProtocol therapyAnalysis populationTrastuzumab emtansineClinical trialsRelevant toxicityPatientsFactor receptorLess toxicityWeeksTrastuzumabCancerPaclitaxel
2020
Primary analysis of KAITLIN: A phase III study of trastuzumab emtansine (T-DM1) + pertuzumab versus trastuzumab + pertuzumab + taxane, after anthracyclines as adjuvant therapy for high-risk HER2-positive early breast cancer (EBC).
Harbeck N, Im S, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis P, Gianni L, Swain S, Im Y, De Laurentiis M, Nowecki Z, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer E, Krop I. Primary analysis of KAITLIN: A phase III study of trastuzumab emtansine (T-DM1) + pertuzumab versus trastuzumab + pertuzumab + taxane, after anthracyclines as adjuvant therapy for high-risk HER2-positive early breast cancer (EBC). Journal Of Clinical Oncology 2020, 38: 500-500. DOI: 10.1200/jco.2020.38.15_suppl.500.Peer-Reviewed Original ResearchHER2-positive early breast cancerInvasive disease-free survivalEarly breast cancerPatient-reported outcomesCo-primary endpointsStandard of careT-DM1ITT populationOverall survivalAnthracycline-based chemotherapyOpen-label studyDisease-free survivalPhase III studyWeeks of surgeryHigh-risk populationChemotherapy-associated toxicityAdjuvant taxanesConcurrent trastuzumabEndocrine therapySecondary endpointsAdjuvant radiotherapyAdjuvant therapyIII studyNodal statusMore patients
2017
SANDPIPER: Phase III study of the PI3-kinase (PI3K) inhibitor taselisib (GDC-0032) plus fulvestrant in patients (pts) with estrogen receptor (ER)-positive, HER2-negative locally advanced or metastatic breast cancer (BC) enriched for pts with PIK3CA- mutant tumors.
Baselga J, Cortés J, DeLaurentiis M, Dent S, Diéras V, Harbeck N, Hsu J, Jin H, Schimmoller F, Wilson T, Im Y, Jacot W, Krop I, Verma S. SANDPIPER: Phase III study of the PI3-kinase (PI3K) inhibitor taselisib (GDC-0032) plus fulvestrant in patients (pts) with estrogen receptor (ER)-positive, HER2-negative locally advanced or metastatic breast cancer (BC) enriched for pts with PIK3CA- mutant tumors. Journal Of Clinical Oncology 2017, 35: tps1119-tps1119. DOI: 10.1200/jco.2017.35.15_suppl.tps1119.Peer-Reviewed Original ResearchPIK3CA-mutant tumorsMetastatic breast cancerBreast cancerPIK3CA mutationsInvestigator-assessed progression-free survivalHER2-negative breast tumorsClinical benefit rateObjective response ratePrimary efficacy endpointProgression-free survivalPatient-reported outcomesAromatase inhibitor treatmentSelective PI3K inhibitorFrequent genomic alterationsProliferation of tumorsBC cell linesPIK3CA mutant breast cancersPI3K inhibitorsEfficacy endpointObjective responseOverall survivalPartial responseVisceral diseaseDisease recurrenceEndocrine sensitivity
2014
Patient-reported outcomes (PROs) from TH3RESA, a phase 3 study of trastuzumab emtansine (T-DM1) versus treatment of physician’s choice (TPC) in patients with pretreated HER2-positive advanced breast cancer.
Bartley K, Wildiers H, Kim S, Krop I, Kang J, Yu R, Leung A, Trudeau C, Gonzalez-Martin A. Patient-reported outcomes (PROs) from TH3RESA, a phase 3 study of trastuzumab emtansine (T-DM1) versus treatment of physician’s choice (TPC) in patients with pretreated HER2-positive advanced breast cancer. Journal Of Clinical Oncology 2014, 32: 153-153. DOI: 10.1200/jco.2014.32.26_suppl.153.Peer-Reviewed Original ResearchT-DM1 armNausea/vomitingEORTC QLQ-C30Patient-reported outcomesTPC armT-DM1QLQ-C30HER2-positive advanced breast cancerCox proportional hazards modelEORTC QLQ-BM22Objective response rateAdvanced breast cancerGlobal health statusPhase 3 studyPost-baseline assessmentProgression-free survivalKaplan-Meier methodCycles of treatmentProportional hazards modelImpact of treatmentDistribution of severityQuality of lifePain progressionQLQ-BM22Pain scores