2024
Outcomes with trastuzumab deruxtecan (T-DXd) by HER2 status and line of treatment in a large real-world database of patients with metastatic breast cancer.
Tarantino P, Lee D, Foldi J, Soulos P, Gross C, Grinda T, Winer E, Lin N, Krop I, Tolaney S, Lustberg M, Sammons S. Outcomes with trastuzumab deruxtecan (T-DXd) by HER2 status and line of treatment in a large real-world database of patients with metastatic breast cancer. Journal Of Clinical Oncology 2024, 42: 1077-1077. DOI: 10.1200/jco.2024.42.16_suppl.1077.Peer-Reviewed Original ResearchReal-world progression-free survivalLines of therapyMetastatic breast cancerMedian real-world progression-free survivalT-DXdHER2+Overall survivalHER2-lowHER2- patientsBreast cancerHER2- metastatic breast cancerTreat metastatic breast cancerProgression-free survivalKaplan-Meier methodLines of treatmentDatabase of patientsRetrospective observational studyClinical trial settingHER2 casesIHC 0Trastuzumab deruxtecanHR statusHER2 statusTriple-negativeMedian age
2023
Prognostic and Predictive Value of Immune-Related Gene Expression Signatures vs Tumor-Infiltrating Lymphocytes in Early-Stage ERBB2/HER2-Positive Breast Cancer
Fernandez-Martinez A, Pascual T, Singh B, Nuciforo P, Rashid N, Ballman K, Campbell J, Hoadley K, Spears P, Pare L, Brasó-Maristany F, Chic N, Krop I, Partridge A, Cortés J, Llombart-Cussac A, Prat A, Perou C, Carey L. Prognostic and Predictive Value of Immune-Related Gene Expression Signatures vs Tumor-Infiltrating Lymphocytes in Early-Stage ERBB2/HER2-Positive Breast Cancer. JAMA Oncology 2023, 9: 490-499. PMID: 36602784, PMCID: PMC9857319, DOI: 10.1001/jamaoncol.2022.6288.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsFemaleGene Expression ProfilingHumansImmunoglobulin GLapatinibLymphocytes, Tumor-InfiltratingMiddle AgedNeoadjuvant TherapyPaclitaxelPrognosisRandomized Controlled Trials as TopicReceptor, ErbB-2TranscriptomeTrastuzumabTreatment OutcomeConceptsEvent-free survivalHER2-positive breast cancerPathologic complete responseERBB2/HER2-positive breast cancerPrimary end pointGene expression signaturesBreast cancerEnd pointImmune signaturesPretreatment tumorPrognostic valueExpression signaturesHigher pathologic complete responseMultivariable Cox modelSecondary end pointsAdditive prognostic valueTumor-Infiltrating LymphocytesIntrinsic tumor subtypesWeekly paclitaxelNeoadjuvant treatmentClinicopathologic factorsComplete responseCox analysisMedian ageImmune activationTucatinib vs Placebo, Both in Combination With Trastuzumab and Capecitabine, for Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer in Patients With Brain Metastases
Lin N, Murthy R, Abramson V, Anders C, Bachelot T, Bedard P, Borges V, Cameron D, Carey L, Chien A, Curigliano G, DiGiovanna M, Gelmon K, Hortobagyi G, Hurvitz S, Krop I, Loi S, Loibl S, Mueller V, Oliveira M, Paplomata E, Pegram M, Slamon D, Zelnak A, Ramos J, Feng W, Winer E. Tucatinib vs Placebo, Both in Combination With Trastuzumab and Capecitabine, for Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer in Patients With Brain Metastases. JAMA Oncology 2023, 9: 197-205. PMID: 36454580, PMCID: PMC9716438, DOI: 10.1001/jamaoncol.2022.5610.Peer-Reviewed Original ResearchConceptsErbB2-positive metastatic breast cancerMetastatic breast cancerPlacebo-combination groupPositive metastatic breast cancerNew brain lesionsBrain metastasesOverall survivalSubgroup analysisBrain lesionsBreast cancerIntracranial progression-free survivalPlacebo-controlled clinical trialIntracranial objective response rateStable brain metastasesMedian overall survivalObjective response rateProgression-free survivalExploratory subgroup analysisGreater clinical benefitCNS-PFSHER2CLIMB trialIntracranial outcomesFirst progressionMedian ageClinical benefit
2022
Long-term safety of inavolisib (GDC-0077) in an ongoing phase 1/1b study evaluating monotherapy and in combination (combo) with palbociclib and/or endocrine therapy in patients (pts) with PIK3CA-mutated, hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer (BC).
Bedard P, Accordino M, Cervantes A, Gambardella V, Hamilton E, Italiano A, Juric D, Kalinsky K, Krop I, Oliveira M, Saura C, Schmid P, Turner N, Varga A, Shankar N, Schutzman J, Royer-Joo S, Martin M, Jhaveri K. Long-term safety of inavolisib (GDC-0077) in an ongoing phase 1/1b study evaluating monotherapy and in combination (combo) with palbociclib and/or endocrine therapy in patients (pts) with PIK3CA-mutated, hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer (BC). Journal Of Clinical Oncology 2022, 40: 1052-1052. DOI: 10.1200/jco.2022.40.16_suppl.1052.Peer-Reviewed Original ResearchBreast cancerPO QDHormone receptor-positive/HER2-negative metastatic breast cancerFrequent treatment-related adverse eventsFrequent treatment-related grade 3HER2-negative metastatic breast cancerTreatment-related adverse eventsTreatment-related grade 3G3-4 neutropeniaPhase 1/1b studyPhase 3 doseLong-term tolerabilityNew safety signalsOverall study populationPhase 3 studyMetastatic breast cancerPreliminary antitumor activityLong-term safetyFemale ptsEndocrine therapyPrior therapyDose intensityAdverse eventsArm BMedian ageResults from the phase 1/2 study of patritumab deruxtecan, a HER3-directed antibody-drug conjugate (ADC), in patients with HER3-expressing metastatic breast cancer (MBC).
Krop I, Masuda N, Mukohara T, Takahashi S, Nakayama T, Inoue K, Iwata H, Toyama T, Yamamoto Y, Hansra D, Takahashi M, Osaki A, Koyama K, Inoue T, Yonekura T, Mostillo J, Ohwada S, Tanaka Y, Sternberg D, Yonemori K. Results from the phase 1/2 study of patritumab deruxtecan, a HER3-directed antibody-drug conjugate (ADC), in patients with HER3-expressing metastatic breast cancer (MBC). Journal Of Clinical Oncology 2022, 40: 1002-1002. DOI: 10.1200/jco.2022.40.16_suppl.1002.Peer-Reviewed Original ResearchMetastatic breast cancerAntibody-drug conjugatesAnti-HER3 monoclonal antibodyInvestigational antibody-drug conjugateTopoisomerase I inhibitor payloadWhite blood cell countDose-finding portionGrade 5 eventsMedian treatment durationPhase 1/2 studyInterstitial lung diseaseBlood cell countMedian study durationECOG PSData cutoffDose expansionCentral adjudicationMetastatic diseaseNeutrophil countPrior linesMedian agePhase 1/2Platelet countSafety profileLung disease
2021
Chemotherapy-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
2020
TBCRC023: A Randomized Phase II Neoadjuvant Trial of Lapatinib Plus Trastuzumab Without Chemotherapy for 12 versus 24 Weeks in Patients with HER2-Positive Breast Cancer
Rimawi MF, Niravath P, Wang T, Rexer BN, Forero A, Wolff AC, Nanda R, Storniolo AM, Krop I, Goetz MP, Nangia JR, Jiralerspong S, Pavlick A, Veeraraghavan J, De Angelis C, Gutierrez C, Schiff R, Hilsenbeck SG, Osborne CK, Consortium O. TBCRC023: A Randomized Phase II Neoadjuvant Trial of Lapatinib Plus Trastuzumab Without Chemotherapy for 12 versus 24 Weeks in Patients with HER2-Positive Breast Cancer. Clinical Cancer Research 2020, 26: 821-827. PMID: 31662331, DOI: 10.1158/1078-0432.ccr-19-0851.Peer-Reviewed Original ResearchConceptsHER2-positive breast cancerPathologic complete responseDual anti-HER2 therapyAnti-HER2 therapyBreast cancerEstrogen receptorNeoadjuvant trialsPhase II neoadjuvant trialRandomized phase II trialHER2-positive breast tumorsDeescalation of therapyER-positive subgroupMedian tumor sizePhase II trialPhase II designAcneiform rashEvaluable patientsCommon toxicitiesII trialComplete responseMedian ageStudy treatmentTumor sizeExperimental armPatients
2019
Randomized phase II study of eribulin mesylate (E) with or without pembrolizumab (P) for hormone receptor-positive (HR+) metastatic breast cancer (MBC).
Tolaney S, Barroso-Sousa R, Keenan T, Trippa L, Hu J, Luis I, Wulf G, Spring L, Sinclair N, Andrews C, Pittenger J, Richardson E, Dillon D, Lin N, Overmoyer B, Partridge A, VanAllen E, Mittendorf E, Winer E, Krop I. Randomized phase II study of eribulin mesylate (E) with or without pembrolizumab (P) for hormone receptor-positive (HR+) metastatic breast cancer (MBC). Journal Of Clinical Oncology 2019, 37: 1004-1004. DOI: 10.1200/jco.2019.37.15_suppl.1004.Peer-Reviewed Original ResearchProgression-free survivalObjective response rateNeutrophil-lymphocyte ratioTumor-infiltrating lymphocytesTumor mutation burdenOverall survivalPrior linesMedian progression-free survivalCheckpoint inhibitor monotherapyMedian prior linesKey secondary endpointLines of chemotherapyPD-L1 statusTime of progressionChemotherapy 1Eligible patientsHormonal therapyPrimary endpointProtocol therapySecondary endpointsInhibitor monotherapyArm BMedian ageArm ATherapy 2
2017
A mouse-human phase I co-clinical trial of taselisib in combination with TDM1 in advanced HER2-positive breast cancer (MBC).
Metzger Filho O, Goel S, Barry W, Hamilton E, Tolaney S, Yardley D, Rees R, Demeo M, Mills C, Hafner M, Winer E, Zhao J, Krop I. A mouse-human phase I co-clinical trial of taselisib in combination with TDM1 in advanced HER2-positive breast cancer (MBC). Journal Of Clinical Oncology 2017, 35: 1030-1030. DOI: 10.1200/jco.2017.35.15_suppl.1030.Peer-Reviewed Original ResearchPhase Ib studyT-DM1Co-clinical trialsIb studyAdvanced HER2-positive breast cancerT-DM1-resistant cellsHER2-positive breast cancerPR/CRAcceptable safety profileAnti-HER2 therapyPI3K blockadePre-clinical experimentsConfirmed responsesMedian PFSPJP prophylaxisMedian durationMedian agePIK3CA H1047RPIK3CA statusSafety profilePneumocystis pneumoniaHER2 expressionClinical resultsMammary carcinomaBreast cancer
2015
SU2C Phase Ib Study of Paclitaxel and MK-2206 in Advanced Solid Tumors and Metastatic Breast Cancer
Gonzalez-Angulo AM, Krop I, Akcakanat A, Chen H, Liu S, Li Y, Culotta KS, Tarco E, Piha-Paul S, Moulder-Thompson S, Velez-Bravo V, Sahin AA, Doyle LA, Do KA, Winer EP, Mills GB, Kurzrock R, Meric-Bernstam F. SU2C Phase Ib Study of Paclitaxel and MK-2206 in Advanced Solid Tumors and Metastatic Breast Cancer. Journal Of The National Cancer Institute 2015, 107: dju493. PMID: 25688104, PMCID: PMC4342675, DOI: 10.1093/jnci/dju493.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsDrug Administration ScheduleDrug EruptionsFatigueFemaleHeterocyclic Compounds, 3-RingHumansHyperglycemiaMaleMaximum Tolerated DoseMiddle AgedNeoplasmsNeutropeniaPaclitaxelSeverity of Illness IndexTreatment OutcomeConceptsDose escalationDay 1Day 2Higher adverse eventsPhase Ib studyWeeks of therapyAdvanced solid tumorsCTCAE grade 3Metastatic breast cancerPrevious phase IPreliminary antitumor activityDose expansionStable diseaseObjective responseUnacceptable toxicityAdverse eventsMedian ageWeekly dosesClinical benefitPharmacodynamic markersSystemic exposureExcessive toxicityTumor responseGrade 3Median number
2013
A phase II study of bevacizumab in combination with vinorelbine and trastuzumab in HER2-positive metastatic breast cancer
Lin NU, Seah DS, Gelman R, Desantis S, Mayer EL, Isakoff S, DiPiro P, Krop IE, Come SE, Weckstein D, Winer EP, Burstein HJ. A phase II study of bevacizumab in combination with vinorelbine and trastuzumab in HER2-positive metastatic breast cancer. Breast Cancer Research And Treatment 2013, 139: 403-410. PMID: 23645007, DOI: 10.1007/s10549-013-2551-9.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerGrade 3/4 non-hematologic toxicitiesHER2-positive metastatic breast cancerNon-hematologic toxicitiesTreatment-related toxicityBreast cancerCommon treatment-related toxicitiesFirst-line patientsProtocol-based therapySecond-line cohortSecond-line patientsSecond-line settingPhase II studyProportion of patientsCombination of vinorelbineCo-primary endpointsEligible patientsFebrile neutropeniaMedian PFSII studyMedian durationObjective responsePrior linesUnacceptable toxicityMedian age
2012
Results from a phase Ib study of trastuzumab emtansine (T-DM1), paclitaxel (T), and pertuzumab (P) in patients with HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab.
Modi S, Elias A, LoRusso P, Samant M, Guardino E, Althaus B, Krop I. Results from a phase Ib study of trastuzumab emtansine (T-DM1), paclitaxel (T), and pertuzumab (P) in patients with HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab. Journal Of Clinical Oncology 2012, 30: 528-528. DOI: 10.1200/jco.2012.30.15_suppl.528.Peer-Reviewed Original ResearchHER2-positive metastatic breast cancerMetastatic breast cancerT-DM1Prior systemic therapyPhase Ib studyPhase II studyDose-escalation studySingle-agent activityDuration of responseDose escalation schemeFuture clinical trialsDLT criteriaII studyMedian ageSystemic therapyExtension trialPreclinical dataTrastuzumab emtansineClinical trialsMedian numberToxicity CriteriaBreast cancerIb studyPhase IbQ3w