2024
TBCRC 048 (olaparib expanded) expansion cohorts: Phase 2 study of olaparib monotherapy in patients (pts) with metastatic breast cancer (MBC) with germline (g) mutations in PALB2 or somatic (s) mutations in BRCA1 or BRCA2.
Tung N, Robson M, Nanda R, Li T, Vinayak S, Shah P, Khoury K, Kimmick G, Santa-Maria C, Brufsky A, DeMeo M, Vieira J, Carey L, Wulf G, Domchek S, Krop I, Wolff A, Winer E, Garber J. TBCRC 048 (olaparib expanded) expansion cohorts: Phase 2 study of olaparib monotherapy in patients (pts) with metastatic breast cancer (MBC) with germline (g) mutations in PALB2 or somatic (s) mutations in BRCA1 or BRCA2. Journal Of Clinical Oncology 2024, 42: 1021-1021. DOI: 10.1200/jco.2024.42.16_suppl.1021.Peer-Reviewed Original ResearchProgression-free survivalDuration of responseMetastatic breast cancerClinical benefit rateTriple-negative breast cancerMedian duration of responseMedian progression-free survivalMutant allele frequencyExpansion cohortHER2-negativeHER2-positiveCohort 2aNon-respondersBreast cancerEarly due to slow enrollmentMetastatic chemotherapy regimensResponse to olaparibPhase 2 studyPhase II trialKaplan-Meier methodPredictors of responseCohort of womenWilcoxon rank sum testRank sum testBRCA1m
2022
Clinical Efficacy and Whole-Exome Sequencing of Liquid Biopsies in a Phase IB/II Study of Bazedoxifene and Palbociclib in Advanced Hormone Receptor-Positive Breast Cancer.
Tsuji J, Li T, Grinshpun A, Coorens T, Russo D, Anderson L, Rees R, Nardone A, Patterson C, Lennon NJ, Cibulskis C, Leshchiner I, Tayob N, Tolaney SM, Tung N, McDonnell DP, Krop IE, Winer EP, Stewart C, Getz G, Jeselsohn R. Clinical Efficacy and Whole-Exome Sequencing of Liquid Biopsies in a Phase IB/II Study of Bazedoxifene and Palbociclib in Advanced Hormone Receptor-Positive Breast Cancer. Clinical Cancer Research 2022, 28: 5066-5078. PMID: 36215125, PMCID: PMC9722539, DOI: 10.1158/1078-0432.ccr-22-2305.Peer-Reviewed Original ResearchConceptsProgression-free survivalPhase Ib/II studyCombination of palbociclibBreast cancerWhole-exome sequencingESR1 mutationsII studyClinical efficacySafety profileHormone receptor-positive/HER2-negative advanced breast cancerAdvanced hormone receptor-positive breast cancerHER2-negative advanced breast cancerHormone receptor-positive breast cancerThird-generation selective estrogen receptor modulatorMedian progression-free survivalEndocrine-resistant breast cancerReceptor-positive breast cancerShorter progression-free survivalSelective estrogen receptor modulatorsClinical benefit rateAcceptable safety profileAdvanced breast cancerEstrogen receptor modulatorsSelective ER degraderDNA whole-exome sequencing
2021
Phase II Single-Arm Study to Assess Trastuzumab and Vinorelbine in Advanced Breast Cancer Patients With HER2-Negative Tumors and HER2-Positive Circulating Tumor Cells
Parsons HA, Macrae ER, Guo H, Li T, Barry WT, Tayob N, Wulf GM, Isakoff SJ, Krop IE. Phase II Single-Arm Study to Assess Trastuzumab and Vinorelbine in Advanced Breast Cancer Patients With HER2-Negative Tumors and HER2-Positive Circulating Tumor Cells. JCO Precision Oncology 2021, 5: 896-903. PMID: 34994617, PMCID: PMC9848583, DOI: 10.1200/po.20.00461.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerHER2-positive CTCsHER2-negative metastatic breast cancerObjective response rateBreast cancerHER2-Positive Circulating Tumor CellsHER2-positive metastatic breast cancerResponse rateMedian progression-free survivalPhase II single-arm studyProgressive metastatic breast cancerHER2-negative breast cancerAdvanced breast cancer patientsHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Tumor cellsHER2-positive diseasePrior chemotherapy regimenTumor tissue testingClinical benefit ratePrimary end pointPhase II trialProgression-free survivalGrowth factor receptor 2HER2-negative tumorsThe efficacy and safety of enzalutamide with trastuzumab in patients with HER2+ and androgen receptor-positive metastatic or locally advanced breast cancer
Wardley A, Cortes J, Provencher L, Miller K, Chien AJ, Rugo HS, Steinberg J, Sugg J, Tudor IC, Huizing M, Young R, Abramson V, Bose R, Hart L, Chan S, Cameron D, Wright GS, Graas MP, Neven P, Rocca A, Russo S, Krop IE. The efficacy and safety of enzalutamide with trastuzumab in patients with HER2+ and androgen receptor-positive metastatic or locally advanced breast cancer. Breast Cancer Research And Treatment 2021, 187: 155-165. PMID: 33591468, PMCID: PMC8062601, DOI: 10.1007/s10549-021-06109-7.Peer-Reviewed Original ResearchConceptsTreatment-emergent adverse eventsProgression-free survivalSafety of enzalutamideBreast cancerSerious treatment-emergent adverse eventsEastern Cooperative Oncology Group statusMedian progression-free survivalPrior anti-HER2 therapyEnd pointHuman epidermal growth factor receptorClinical benefit rateDurable stable diseaseSolid Tumors v1.1Primary end pointSecondary end pointsAdvanced breast cancerAnti-HER2 therapyHormone receptor statusResponse Evaluation CriteriaSubset of patientsAR expression levelsTrastuzumab-resistant HER2Durable disease controlMalignant neoplasm progressionAnti-HER2 antibody
2020
Phase III randomized study of taselisib or placebo with fulvestrant in estrogen receptor-positive, PIK3CA-mutant, HER2-negative, advanced breast cancer: the SANDPIPER trial ☆
Dent S, Cortés J, Im Y, Diéras V, Harbeck N, Krop IE, Wilson TR, Cui N, Schimmoller F, Hsu JY, He J, De Laurentiis M, Sousa S, Drullinsky P, Jacot W. Phase III randomized study of taselisib or placebo with fulvestrant in estrogen receptor-positive, PIK3CA-mutant, HER2-negative, advanced breast cancer: the SANDPIPER trial ☆. Annals Of Oncology 2020, 32: 197-207. PMID: 33186740, PMCID: PMC8457522, DOI: 10.1016/j.annonc.2020.10.596.Peer-Reviewed Original ResearchConceptsInvestigator-assessed progression-free survivalClinical benefit ratePIK3CA-mutant tumorsObjective response rateSecondary endpointsPrimary endpointObjective responseBenefit rateBreast cancerResponse ratePhase III Randomized StudyDisease recurrence/progressionBlinded independent central reviewPIK3CA mutation statusSerious adverse eventsAdvanced breast cancerProgression-free survivalHealth-related qualityMetastatic breast cancerRecurrence/progressionModest clinical benefitIndependent central reviewSelective PI3K inhibitorPI3K inhibitorsMore discontinuationsPhase 2 study of buparlisib (BKM120), a pan-class I PI3K inhibitor, in patients with metastatic triple-negative breast cancer
Garrido-Castro AC, Saura C, Barroso-Sousa R, Guo H, Ciruelos E, Bermejo B, Gavilá J, Serra V, Prat A, Paré L, Céliz P, Villagrasa P, Li Y, Savoie J, Xu Z, Arteaga CL, Krop IE, Solit DB, Mills GB, Cantley LC, Winer EP, Lin NU, Rodon J. Phase 2 study of buparlisib (BKM120), a pan-class I PI3K inhibitor, in patients with metastatic triple-negative breast cancer. Breast Cancer Research 2020, 22: 120. PMID: 33138866, PMCID: PMC7607628, DOI: 10.1186/s13058-020-01354-y.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAminopyridinesAntineoplastic Combined Chemotherapy ProtocolsClass I Phosphatidylinositol 3-KinasesDisease ProgressionFemaleHigh-Throughput Nucleotide SequencingHumansMiddle AgedMorpholinesNeoplasm MetastasisPatient SafetyProtein Kinase InhibitorsProteomicsResponse Evaluation Criteria in Solid TumorsSurvival RateTreatment OutcomeTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerProgression-free survivalPan-class I PI3K inhibitorMetastatic triple-negative breast cancerStable diseasePhase 2 studyBreast cancerOverall survivalPI3K inhibitorsPI3K pathwayPartial responseComplete responseClinical benefitSingle-arm phase 2 studyTriple-negative metastatic breast cancerMedian progression-free survivalK inhibitorsClinical benefit rateEfficacy of buparlisibK pathwayFrequent adverse eventsMedian overall survivalPercent of patientsMetastatic breast cancerSubset of patientsTBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes.
Tung NM, Robson ME, Ventz S, Santa-Maria CA, Nanda R, Marcom PK, Shah PD, Ballinger TJ, Yang ES, Vinayak S, Melisko M, Brufsky A, DeMeo M, Jenkins C, Domchek S, D'Andrea A, Lin NU, Hughes ME, Carey LA, Wagle N, Wulf GM, Krop IE, Wolff AC, Winer EP, Garber JE. TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes. Journal Of Clinical Oncology 2020, 38: 4274-4282. PMID: 33119476, DOI: 10.1200/jco.20.02151.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerObjective response rateProgression-free survivalPoly (ADP-ribose) polymerase (PARP) inhibitorsPhase II studyBreast cancerMutation carriersII studyMedian progression-free survivalNegative metastatic breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Clinical benefit rateHER2-negative diseasePlatinum-refractory diseaseGrowth factor receptor 2Population of patientsFactor receptor 2Homologous recombination-related genesConfirmed responsesEligible patientsMeasurable diseaseSecondary endpointsChemotherapy regimensPrimary endpointPhase 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 activityA phase Ib study of pembrolizumab (pembro) plus trastuzumab emtansine (T-DM1) for metastatic HER2+ breast cancer (MBC).
Waks A, Keenan T, Li T, Tayob N, Wulf G, Richardson E, Mittendorf E, Overmoyer B, Krop I, Winer E, Van Allen E, Agudo J, Tolaney S. A phase Ib study of pembrolizumab (pembro) plus trastuzumab emtansine (T-DM1) for metastatic HER2+ breast cancer (MBC). Journal Of Clinical Oncology 2020, 38: 1046-1046. DOI: 10.1200/jco.2020.38.15_suppl.1046.Peer-Reviewed Original ResearchObjective response rateProgression-free survivalAdverse eventsT-DM1PD-L1 combined positive scoreTumor-infiltrating lymphocyte (TIL) statusClinical benefit rateDose-finding cohortMedian age 54Phase 2 dosePhase Ib studyCombined positive scoreAnti-PD1 antibodyPhase 1 trialDe-escalation designEligible patientsLymphocyte statusMetastatic HER2Expansion cohortOral mucositisPrimary endpointSecondary endpointsAntitumor immunityImmune signaturesPrior linesTBCRC 048: A phase II study of olaparib monotherapy in metastatic breast cancer patients with germline or somatic mutations in DNA damage response (DDR) pathway genes (Olaparib Expanded).
Tung N, Robson M, Ventz S, Santa-Maria C, Marcom P, Nanda R, Shah P, Ballinger T, Yang E, Melisko M, Brufsky A, Vinayak S, Demeo M, Jenkins C, Domchek S, Wulf G, Krop I, Wolff A, Winer E, Garber J. TBCRC 048: A phase II study of olaparib monotherapy in metastatic breast cancer patients with germline or somatic mutations in DNA damage response (DDR) pathway genes (Olaparib Expanded). Journal Of Clinical Oncology 2020, 38: 1002-1002. DOI: 10.1200/jco.2020.38.15_suppl.1002.Peer-Reviewed Original Research
2019
Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer
Modi S, Saura C, Yamashita T, Park YH, Kim SB, Tamura K, Andre F, Iwata H, Ito Y, Tsurutani J, Sohn J, Denduluri N, Perrin C, Aogi K, Tokunaga E, Im SA, Lee KS, Hurvitz SA, Cortes J, Lee C, Chen S, Zhang L, Shahidi J, Yver A, Krop I. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. New England Journal Of Medicine 2019, 382: 610-621. PMID: 31825192, PMCID: PMC7458671, DOI: 10.1056/nejmoa1914510.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCamptothecinConsolidation ChemotherapyFemaleHumansImmunoconjugatesIntention to Treat AnalysisKaplan-Meier EstimateLung Diseases, InterstitialMiddle AgedProgression-Free SurvivalReceptor, ErbB-2TrastuzumabConceptsHER2-positive metastatic breast cancerMetastatic breast cancerHER2-positive breast cancerProgression-free survivalTrastuzumab deruxtecanInterstitial lung diseaseBreast cancerMedian durationLung diseaseTrastuzumab emtansinePhase 1 dose-finding studyAdvanced HER2-positive breast cancerKey secondary end pointEnd pointPrevious treatmentClinical benefit rateDecreased neutrophil countCommon adverse eventsDisease control rateMedian response durationPrimary end pointSecondary end pointsPhase 2 studySubgroup of patientsDurable antitumor activityA phase Ib, open-label, dose-escalation study of the safety and pharmacology of taselisib (GDC-0032) in combination with either docetaxel or paclitaxel in patients with HER2-negative, locally advanced, or metastatic breast cancer
Abramson VG, Oliveira M, Cervantes A, Wildiers H, Patel MR, Bauer TM, Bedard PL, Becerra C, Richey S, Wei MC, Reyner E, Bond J, Cui N, Wilson TR, Moore HM, Saura C, Krop IE. A phase Ib, open-label, dose-escalation study of the safety and pharmacology of taselisib (GDC-0032) in combination with either docetaxel or paclitaxel in patients with HER2-negative, locally advanced, or metastatic breast cancer. Breast Cancer Research And Treatment 2019, 178: 121-133. PMID: 31368034, DOI: 10.1007/s10549-019-05360-3.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCarcinoma, Non-Small-Cell LungClass I Phosphatidylinositol 3-KinasesDocetaxelFemaleHumansImidazolesLung NeoplasmsMaleMaximum Tolerated DoseMiddle AgedMutationNeoplasm MetastasisOxazepinesPaclitaxelReceptor, ErbB-2Survival AnalysisTreatment OutcomeConceptsNon-small cell lung cancerDose-limiting toxicityMetastatic breast cancerAdverse eventsBreast cancerPhase IbClinical benefit rateDose-expansion studyObjective response ratePhase II doseSerious adverse eventsDose-escalation studyCell lung cancerBenefit-risk profileDays on/2ResultsEighty patientsPrimary endpointSecondary endpointsSafety profileLung cancerBenefit ratePatientsSingle agentResponse rateDocetaxel
2018
Phase III study of taselisib (GDC-0032) + fulvestrant (FULV) v FULV in patients (pts) with estrogen receptor (ER)-positive, PIK3CA -mutant (MUT), locally advanced or metastatic breast cancer (MBC): Primary analysis from SANDPIPER.
Baselga J, Dent S, Cortés J, Im Y, Diéras V, Harbeck N, Krop I, Verma S, Wilson T, Jin H, Wang L, Schimmoller F, Hsu J, He J, DeLaurentiis M, Drullinsky P, Jacot W. Phase III study of taselisib (GDC-0032) + fulvestrant (FULV) v FULV in patients (pts) with estrogen receptor (ER)-positive, PIK3CA -mutant (MUT), locally advanced or metastatic breast cancer (MBC): Primary analysis from SANDPIPER. Journal Of Clinical Oncology 2018, 36: lba1006-lba1006. DOI: 10.1200/jco.2018.36.18_suppl.lba1006.Peer-Reviewed Original ResearchInvestigator-assessed progression-free survivalMetastatic breast cancerClinical benefit rateObjective response rateOverall survivalBlinded independent central reviewProgression-free survivalIndependent central reviewDose of treatmentSelective PI3K inhibitorBC cell linesPI3K inhibitorsTreat populationPrimary endpointSecondary endpointsAdverse eventsObjective responsePartial responseVisceral diseaseDisease recurrenceEndocrine sensitivityCentral reviewSafety profileAromatase inhibitorsBenefit rate
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 sensitivityA randomized, double-blinded, controlled study of tucatinib (ONT-380) vs. placebo in combination with capecitabine (C) and trastuzumab (Tz) in patients with pretreated HER2+ unresectable locally advanced or metastatic breast carcinoma (mBC) (HER2CLIMB).
Anders C, Murthy R, Hamilton E, Borges V, Cameron D, Carey L, Müller V, Curigliano G, Gelmon K, Hortobagyi G, Krop I, Loibl S, Pivot X, Pegram M, Slamon D, Hurvitz S, Tsai M, Winer E. A randomized, double-blinded, controlled study of tucatinib (ONT-380) vs. placebo in combination with capecitabine (C) and trastuzumab (Tz) in patients with pretreated HER2+ unresectable locally advanced or metastatic breast carcinoma (mBC) (HER2CLIMB). Journal Of Clinical Oncology 2017, 35: tps1107-tps1107. DOI: 10.1200/jco.2017.35.15_suppl.tps1107.Peer-Reviewed Original ResearchProgression-free survivalMetastatic breast carcinomaBrain metsIndependent data monitoring committeeClinical benefit ratePhase 1b studyDuration of responseIndependent central reviewPrimary study objectiveData monitoring committeeCNS progressionEGFR agentsPo bidBrain metastasesAdult patientsObjective responseOverall survivalCentral reviewStudy treatmentT-DM1CNS therapyTrastuzumab emtansineBenefit rateSelective small molecule inhibitorsBreast carcinoma
2016
Phase 1b/2a study of trastuzumab emtansine (T-DM1), paclitaxel, and pertuzumab in HER2-positive metastatic breast cancer
Krop IE, Modi S, LoRusso PM, Pegram M, Guardino E, Althaus B, Lu D, Strasak A, Elias A. Phase 1b/2a study of trastuzumab emtansine (T-DM1), paclitaxel, and pertuzumab in HER2-positive metastatic breast cancer. Breast Cancer Research 2016, 18: 34. PMID: 26979312, PMCID: PMC4791863, DOI: 10.1186/s13058-016-0691-7.Peer-Reviewed Original ResearchConceptsClinical benefit ratePhase 1b/2a studyObjective response rateT-DM1Adverse eventsPaclitaxel dosesPeripheral neuropathyBreast cancerHER2-positive advanced breast cancerHER2-positive metastatic breast cancerPhase 2aPhase 1bGrade adverse eventsT-DM1 3.6Advanced breast cancerMetastatic breast cancerDose-escalation approachPre-clinical studiesAnti-tumor activityConclusionsThis regimenExperienced gradeMeasurable diseasePaclitaxel 80Prior therapyResultsThe MTD
2015
Phase II Study of Lapatinib in Combination With Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer: Clinical Outcomes and Predictive Value of Early [18F]Fluorodeoxyglucose Positron Emission Tomography Imaging (TBCRC 003)
Lin NU, Guo H, Yap JT, Mayer IA, Falkson CI, Hobday TJ, Dees EC, Richardson AL, Nanda R, Rimawi MF, Ryabin N, Najita JS, Barry WT, Arteaga CL, Wolff AC, Krop IE, Winer EP, Van den Abbeele AD. Phase II Study of Lapatinib in Combination With Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer: Clinical Outcomes and Predictive Value of Early [18F]Fluorodeoxyglucose Positron Emission Tomography Imaging (TBCRC 003). Journal Of Clinical Oncology 2015, 33: 2623-2631. PMID: 26169615, PMCID: PMC4534525, DOI: 10.1200/jco.2014.60.0353.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCohort StudiesFemaleFluorodeoxyglucose F18HumansLapatinibMiddle AgedNeoplasm MetastasisPositron-Emission TomographyQuinazolinesReceptor, ErbB-2TrastuzumabTreatment OutcomeConceptsMetastatic breast cancerHuman epidermal growth factor receptorClinical benefit rateEpidermal growth factor receptorObjective response rateProgression-free survivalGrowth factor receptorClinical outcomesWeek 1Cohort 2Benefit rateCohort 1Breast cancerFactor receptorPredictive valueResponse rateConfirmed objective response rateMedian progression-free survivalEnd pointPhase II studyPrimary end pointSecondary end pointsSelection of patientsToxicity of chemotherapyPET/CT
2013
A phase II study of ixabepilone and trastuzumab for metastatic HER2-positive breast cancer
Tolaney SM, Najita J, Sperinde J, Huang W, Chen WY, Savoie J, Fornier M, Winer EP, Bunnell C, Krop IE. A phase II study of ixabepilone and trastuzumab for metastatic HER2-positive breast cancer. Annals Of Oncology 2013, 24: 1841-1847. PMID: 23559151, PMCID: PMC3690910, DOI: 10.1093/annonc/mdt121.Peer-Reviewed Original ResearchConceptsMetastatic HER2-positive breast cancerHER2-positive breast cancerCombination of ixabepilonePhase II studyBreast cancerII studyMetastatic diseaseCohort 2Cohort 1Treatment-related toxic effectsClinical benefit rateSubsequent-line therapyTrastuzumab-containing regimensMetastatic breast cancerPrior chemotherapyLine therapyBenefit rateOverall RRDay 1PatientsTrastuzumabIxabepiloneCancerTumor biomarkersCohort
2012
LBA12 Results from Emilia, A Phase 3 Study of Trastuzumab Emtansine (T-DM1) vs Capecitabine (X) and Lapatinib (L) in Her2-Positive Locally Advanced or Metastatic Breast Cancer (MBC)
Verma S, Miles D, Gianni L, Krop I, Welslau M, Baselga J, Pegram M, Oh D, Diéras V, Guardino E, Fang L, Lu M, Olsen S, Blackwell K. LBA12 Results from Emilia, A Phase 3 Study of Trastuzumab Emtansine (T-DM1) vs Capecitabine (X) and Lapatinib (L) in Her2-Positive Locally Advanced or Metastatic Breast Cancer (MBC). Annals Of Oncology 2012, 23: ixe5-ixe6. DOI: 10.1016/s0923-7534(20)34362-3.Peer-Reviewed Original ResearchProgression-free survivalGenentech/RocheMetastatic breast cancerClinical benefit rateSecondary end pointsT-DM1Overall survivalEnd pointObjective responseTreatment failureBenefit ratePrior treatmentKey secondary end pointInterim overall survivalObjective response ratePrimary end pointSubgroups of ptsHormone receptor statusStudy end pointPhase 3 studyDuration of responsePotential new therapiesFinal PFS analysisCardiac AEsMBC therapyA phase 1 study of weekly dosing of trastuzumab emtansine (T‐DM1) in patients with advanced human epidermal growth factor 2–positive breast cancer
Beeram M, Krop IE, Burris HA, Girish SR, Yu W, Lu MW, Holden SN, Modi S. A phase 1 study of weekly dosing of trastuzumab emtansine (T‐DM1) in patients with advanced human epidermal growth factor 2–positive breast cancer. Cancer 2012, 118: 5733-5740. PMID: 22648179, DOI: 10.1002/cncr.27622.Peer-Reviewed Original ResearchConceptsHER2-positive metastatic breast cancerMetastatic breast cancerAdverse eventsT-DM1Breast cancerTrastuzumab emtansineObjective partial tumor responseTreatment-related adverse eventsClinical benefit rateDose-escalation studyPartial tumor responsePhase 1 studyTotal trastuzumabDose modificationMedian durationWeekly doseWeekly dosingAdditional patientsTumor responseBenefit rateHuman epidermal growth factorEpidermal growth factorPatientsGrowth factorAntitumor activity