2023
Patritumab Deruxtecan (HER3-DXd), a Human Epidermal Growth Factor Receptor 3–Directed Antibody-Drug Conjugate, in Patients With Previously Treated Human Epidermal Growth Factor Receptor 3–Expressing Metastatic Breast Cancer: A Multicenter, Phase I/II Trial
Krop I, Masuda N, Mukohara T, Takahashi S, Nakayama T, Inoue K, Iwata H, Yamamoto Y, Alvarez R, Toyama T, Takahashi M, Osaki A, Saji S, Sagara Y, O'Shaughnessy J, Ohwada S, Koyama K, Inoue T, Li L, Patel P, Mostillo J, Tanaka Y, Sternberg D, Sellami D, Yonemori K. Patritumab Deruxtecan (HER3-DXd), a Human Epidermal Growth Factor Receptor 3–Directed Antibody-Drug Conjugate, in Patients With Previously Treated Human Epidermal Growth Factor Receptor 3–Expressing Metastatic Breast Cancer: A Multicenter, Phase I/II Trial. Journal Of Clinical Oncology 2023, 41: 5550-5560. PMID: 37801674, PMCID: PMC10730028, DOI: 10.1200/jco.23.00882.Peer-Reviewed Original ResearchConceptsTreatment-emergent adverse eventsHuman epidermal growth factor receptor 3Epidermal growth factor receptor 3Metastatic breast cancerGrowth factor receptor 3Breast cancerReceptor 3Dose expansionPrevious therapyClinical subtypesCommon treatment-emergent adverse eventsPhase I/II trialHER2-positive breast cancerTriple-negative breast cancerDose-escalation partDose-expansion partManageable safety profileAdvanced breast cancerEpidermal growth factor receptorAntibody-drug conjugatesGrowth factor receptorAdvanced diseaseHematologic toxicityII trialObjective response
2021
331TiP HER2CLIMB-04: Phase II trial of tucatinib + trastuzumab deruxtecan in patients with HER2+ locally advanced or metastatic breast cancer with and without brain metastases
Carey L, Krop I, Ramos J, Feng W, Hamilton E. 331TiP HER2CLIMB-04: Phase II trial of tucatinib + trastuzumab deruxtecan in patients with HER2+ locally advanced or metastatic breast cancer with and without brain metastases. Annals Of Oncology 2021, 32: s510-s511. DOI: 10.1016/j.annonc.2021.08.614.Peer-Reviewed Original Research279P Trastuzumab deruxtecan (T-DXd) in patients with HER2-positive metastatic breast cancer (MBC): Updated survival results from a phase II trial (DESTINY-Breast01)
Manich C, Modi S, Krop I, Park Y, Kim S, Tamura K, André F, Iwata H, Ito Y, Tsurutani J, Sohn J, Lee C, Liu Y, Cathcart J, Singh J, Yamashita T. 279P Trastuzumab deruxtecan (T-DXd) in patients with HER2-positive metastatic breast cancer (MBC): Updated survival results from a phase II trial (DESTINY-Breast01). Annals Of Oncology 2021, 32: s485-s486. DOI: 10.1016/j.annonc.2021.08.562.Peer-Reviewed Original Research128TiP HER2CLIMB-04: Phase II trial of tucatinib + trastuzumab deruxtecan in patients with HER2+ unresectable locally-advanced or metastatic breast cancer with and without brain metastases
Hamilton E, Ramos J, Feng W, Krop I. 128TiP HER2CLIMB-04: Phase II trial of tucatinib + trastuzumab deruxtecan in patients with HER2+ unresectable locally-advanced or metastatic breast cancer with and without brain metastases. Annals Of Oncology 2021, 32: s76. DOI: 10.1016/j.annonc.2021.03.142.Peer-Reviewed Original Research
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 eventsTBCRC 031: Randomized Phase II Study of Neoadjuvant Cisplatin Versus Doxorubicin-Cyclophosphamide in Germline BRCA Carriers With HER2-Negative Breast Cancer (the INFORM trial).
Tung N, Arun B, Hacker MR, Hofstatter E, Toppmeyer DL, Isakoff SJ, Borges V, Legare RD, Isaacs C, Wolff AC, Marcom PK, Mayer EL, Lange PB, Goss AJ, Jenkins C, Krop IE, Winer EP, Schnitt SJ, Garber JE. TBCRC 031: Randomized Phase II Study of Neoadjuvant Cisplatin Versus Doxorubicin-Cyclophosphamide in Germline BRCA Carriers With HER2-Negative Breast Cancer (the INFORM trial). Journal Of Clinical Oncology 2020, 38: 1539-1548. PMID: 32097092, PMCID: PMC8462533, DOI: 10.1200/jco.19.03292.Peer-Reviewed Original ResearchConceptsHER2-negative breast cancerTriple-negative breast cancerResidual cancer burden scoreBreast cancerDoxorubicin-cyclophosphamideRisk ratioStage IPathologic complete response rateHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Single-agent cisplatinComplete response ratePhase II studyPhase II trialGrowth factor receptor 2Positive breast cancerNegative breast cancerFactor receptor 2CT1-3II trialII studyNodal involvementPCR rateNegative diseasePathologic responseTBCRC023: 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
Identifying ERBB2 Activating Mutations in HER2-Negative Breast Cancer: Clinical Impact of Institute-Wide Genomic Testing and Enrollment in Matched Therapy Trials.
Exman P, Garrido-Castro AC, Hughes ME, Freedman RA, Li T, Trippa L, Bychkovsky BL, Barroso-Sousa R, Di Lascio S, Mackichan C, Lloyd MR, Krevalin M, Cerami E, Merrill MS, Santiago R, Crowley L, Kuhnly N, Files J, Lindeman NI, MacConaill LE, Kumari P, Tolaney SM, Krop IE, Bose R, Johnson BE, Ma CX, Dillon DA, Winer EP, Wagle N, Lin NU. Identifying ERBB2 Activating Mutations in HER2-Negative Breast Cancer: Clinical Impact of Institute-Wide Genomic Testing and Enrollment in Matched Therapy Trials. JCO Precision Oncology 2019, 3: 1-9. PMID: 32923853, PMCID: PMC7446367, DOI: 10.1200/po.19.00087.Peer-Reviewed Original ResearchMetastatic breast cancerEligible patientsBreast cancerExact testHER2-negative breast cancerOngoing phase II trialGenomic profilingPhase II trialProportion of patientsComprehensive genomic profilingRoutine clinical practiceFisher's exact testGenomic tumor profilingArchived tissue samplesII trialMedian timeTRIAL REGISTRATIONTrial participationClinical trialsSpecific genomic changesClinical impactGenomic testing resultsRare subsetPatientsClinical practice
2018
A randomized phase II trial of carboplatin with or without nivolumab in first- or second-line metastatic TNBC.
Garrido-Castro A, Barry W, Traina T, Wesolowski R, Tung N, Keenan T, Van Allen E, Lin N, Winer E, Krop I, Tolaney S. A randomized phase II trial of carboplatin with or without nivolumab in first- or second-line metastatic TNBC. Journal Of Clinical Oncology 2018, 36: tps1118-tps1118. DOI: 10.1200/jco.2018.36.15_suppl.tps1118.Peer-Reviewed Original Research
2017
TBCRC 022: Phase II trial of neratinib + capecitabine for patients (Pts) with human epidermal growth factor receptor 2 (HER2+) breast cancer brain metastases (BCBM).
Freedman R, Gelman R, Melisko M, Anders C, Moy B, Blackwell K, Connolly R, Niravath P, Van Poznak C, Puhalla S, Farooq S, Cropp A, Cotter C, Liu M, Krop I, Nangia J, Tung N, Wolff A, Winer E, Lin N. TBCRC 022: Phase II trial of neratinib + capecitabine for patients (Pts) with human epidermal growth factor receptor 2 (HER2+) breast cancer brain metastases (BCBM). Journal Of Clinical Oncology 2017, 35: 1005-1005. DOI: 10.1200/jco.2017.35.15_suppl.1005.Peer-Reviewed Original ResearchBreast cancer brain metastasesObjective response rateCombination of neratinibCentral nervous system (CNS) objective response rateCNS objective response rateNeurologic signs/symptomsGrade 3 toxicityGrade 4 toxicityMedian age 51Cancer brain metastasesPhase II trialSigns/symptomsEvidence-based treatmentsNon-CNS lesionsCNS progressionPrior lapatinibPrior WBRTPrimary endpointProtocol therapyBrain metastasesII trialCNS lesionsNew lesionsMedian numberBrain MRI
2014
TBCRC 022: Phase II trial of neratinib for patients (Pts) with human epidermal growth factor receptor 2 (HER2+) breast cancer and brain metastases (BCBM).
Freedman R, Gelman R, Wefel J, Krop I, Melisko M, Lowe A, Agar N, Blackwell K, Connolly R, Niravath P, Van Poznak C, Puhalla S, Ryabin N, Lawler E, Ibrahim N, Liu M, Wolff A, Winer E, Lin N. TBCRC 022: Phase II trial of neratinib for patients (Pts) with human epidermal growth factor receptor 2 (HER2+) breast cancer and brain metastases (BCBM). Journal Of Clinical Oncology 2014, 32: 528-528. DOI: 10.1200/jco.2014.32.15_suppl.528.Peer-Reviewed Original Research
2013
Phase II trial of carboplatin (C) and bevacizumab (BEV) in patients (pts) with breast cancer brain metastases (BCBM).
Lin N, Gelman R, Younger W, Sohl J, Freedman R, Sorensen A, Bullitt E, Harris G, Morganstern D, Schneider B, Krop I, Winer E. Phase II trial of carboplatin (C) and bevacizumab (BEV) in patients (pts) with breast cancer brain metastases (BCBM). Journal Of Clinical Oncology 2013, 31: 513-513. DOI: 10.1200/jco.2013.31.15_suppl.513.Peer-Reviewed Original ResearchBreast cancer brain metastasesCNS responseDay 1CNS objective response rateNon-target lesionsObjective response rateAnti-edema effectCancer brain metastasesPhase II trialProgressive neurologic signsStandard brain MRINon-CNS diseasesMultiple tumor typesPrior lapatinibPrior trastuzumabRECIST 1.0Steroid dosePrimary endpointProtocol therapyBrain metastasesFirst doseII trialCNS lesionsOverall survivalPartial response
2011
TBCRC 003: Phase II trial of trastuzumab (T) and lapatinib (L) in patients (pts) with HER2+ metastatic breast cancer (MBC).
Lin N, Mayer I, Najita J, Hobday T, Falkson C, Dees E, Rimawi M, Nanda R, Gelman R, Josephs K, Richardson A, Flores L, Van Den Abbeele A, Yap J, Arteaga C, Wolff A, Krop I, Winer E. TBCRC 003: Phase II trial of trastuzumab (T) and lapatinib (L) in patients (pts) with HER2+ metastatic breast cancer (MBC). Journal Of Clinical Oncology 2011, 29: 527-527. DOI: 10.1200/jco.2011.29.15_suppl.527.Peer-Reviewed Original Research
2010
Phase I/II trial of everolimus (RAD001) and trastuzumab in patients with trastuzumab-resistant, HER2-overexpressing breast cancer.
Morrow P, Wulf G, Booser D, Moore J, Flores P, Krop I, Winer E, Hortobagyi G, Yu D, Esteva F. Phase I/II trial of everolimus (RAD001) and trastuzumab in patients with trastuzumab-resistant, HER2-overexpressing breast cancer. Journal Of Clinical Oncology 2010, 28: 1014-1014. DOI: 10.1200/jco.2010.28.15_suppl.1014.Peer-Reviewed Original ResearchPhase II trial of preoperative vinorelbine/trastuzumab (VH) or docetaxel/carboplatin/trastuzumab (TCH) in HER2-positive breast cancer with analysis of resistance mechanisms.
Krop I, Flores L, Tuck D, Ryan P, Partridge A, Morganstern D, Najita J, lezon-Geyda K, Winer E, Harris L. Phase II trial of preoperative vinorelbine/trastuzumab (VH) or docetaxel/carboplatin/trastuzumab (TCH) in HER2-positive breast cancer with analysis of resistance mechanisms. Journal Of Clinical Oncology 2010, 28: 549-549. DOI: 10.1200/jco.2010.28.15_suppl.549.Peer-Reviewed Original ResearchTBCRC 003: Phase II trial of trastuzumab (T) and lapatinib (L) in patients (pts) with HER2+ metastatic breast cancer (MBC).
Lin N, Mayer I, Hobday T, Falkson C, Dees E, Nanda R, Krop I, Rimawi M, Wolff A, Winer E. TBCRC 003: Phase II trial of trastuzumab (T) and lapatinib (L) in patients (pts) with HER2+ metastatic breast cancer (MBC). Journal Of Clinical Oncology 2010, 28: tps132-tps132. DOI: 10.1200/jco.2010.28.15_suppl.tps132.Peer-Reviewed Original Research
2009
A phase I study of weekly dosing of trastuzumab-DM1 (T-DM1) in patients with advanced HER2+ breast cancer.
Krop I, Mita M, Burris H, Birkner M, Girish S, Tibbitts J, Holden S, Lutzker S, Modi S. A phase I study of weekly dosing of trastuzumab-DM1 (T-DM1) in patients with advanced HER2+ breast cancer. Cancer Research 2009, 69: 3136. DOI: 10.1158/0008-5472.sabcs-3136.Peer-Reviewed Original ResearchTrastuzumab-DM1Advanced HER2Antibody-drug conjugatesBreast cancerChemotherapy regimenCycle 1 day 1HER2 antibody-drug conjugatesFirst antibody-drug conjugatePhase IActivity of trastuzumabGrade 4 thrombocytopeniaReversible transaminase elevationT-DM1 exposureDose-escalation studyPhase II trialMeasurable diseaseQ3W dosingTransaminase elevationEscalation studyII trialPartial responseWeekly dosingCardiac toxicityTumor responseClinical trials