2024
182MO Trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice (TPC) in patients (pts) with HER2+ metastatic breast cancer (mBC) previously treated with trastuzumab emtansine (T-DM1): Updated overall survival (OS) results of the randomized phase III DESTINY-breast (DB-)02 study
Kim S, André F, Takano T, Fehm T, Park Y, Lee J, Borges G, Kaplan M, Kaczmarek E, Guarneri V, Yonemori K, Pluard T, Prat A, Paterson F, Oakman C, Nakatani S, Ashfaque S, Lu W, Egorov A, Krop I. 182MO Trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice (TPC) in patients (pts) with HER2+ metastatic breast cancer (mBC) previously treated with trastuzumab emtansine (T-DM1): Updated overall survival (OS) results of the randomized phase III DESTINY-breast (DB-)02 study. ESMO Open 2024, 9: 103204. DOI: 10.1016/j.esmoop.2024.103204.Peer-Reviewed Original Research
2022
Corrigendum to “Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2D metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis” [Annals of Oncology 33 (2022) 321-329]
Curigliano G, Mueller V, Borges V, Hamilton E, Hurvitz S, Loi S, Murthy R, Okines A, Paplomata E, Cameron D, Carey L, Gelmon K, Hortobagyi G, Krop I, Loibl S, Pegram M, Slamon D, Ramos J, Feng W, Winer E. Corrigendum to “Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2D metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis” [Annals of Oncology 33 (2022) 321-329]. Annals Of Oncology 2022, 34: 630. PMID: 36564285, DOI: 10.1016/j.annonc.2022.12.005.Peer-Reviewed Original Research
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 dataMonthsAmenorrheaEmtansineMenopauseTrastuzumabAdjuvant 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 toxicityWeeksTrastuzumabCancerPaclitaxel42O Biomarker analysis from KAITLIN, a randomised phase III study of adjuvant trastuzumab emtansine (TDM-1; K) plus pertuzumab (P) versus trastuzumab (H) plus taxane (T) plus P after anthracyclines (AC) for high-risk HER2-positive early breast cancer (EBC)
Metzger O, Lambertini C, Krop I, Phillips G, Perou C, Symmans F, Melero I, Harbeck N, Winer E, Im S, Barrios C, Bonnefoi H, Gralow J, Ellis P, Gianni L, Toi M, Swain S, Boulet T, Song C, de Haas S. 42O Biomarker analysis from KAITLIN, a randomised phase III study of adjuvant trastuzumab emtansine (TDM-1; K) plus pertuzumab (P) versus trastuzumab (H) plus taxane (T) plus P after anthracyclines (AC) for high-risk HER2-positive early breast cancer (EBC). Annals Of Oncology 2021, 32: s37-s38. DOI: 10.1016/j.annonc.2021.03.056.Peer-Reviewed Original Research
2020
Management of adverse events in patients with HER2+ metastatic breast cancer treated with tucatinib, trastuzumab, and capecitabine (HER2CLIMB).
Okines A, Paplomata E, Wahl T, Wright G, Sutherland S, Jakobsen E, Valdes F, Chan A, Clark A, Conlin A, Lustberg M, Specht J, Pluard T, Zhu X, Krop I, Gelmon K, Slamon D, Ramos J, An G, Hamilton E. Management of adverse events in patients with HER2+ metastatic breast cancer treated with tucatinib, trastuzumab, and capecitabine (HER2CLIMB). Journal Of Clinical Oncology 2020, 38: 1043-1043. DOI: 10.1200/jco.2020.38.15_suppl.1043.Peer-Reviewed Original ResearchAdverse eventsMedian timeControl armBreast cancerExposure-adjusted incidence ratesElevated liver enzymesMetastatic breast cancerCases of diarrheaMedian durationDose modificationTx groupIncidence rateLiver enzymesHigh incidenceDiarrheaTucatinibFirst onsetCapecitabineTrastuzumabHER2Significant inhibitionBilirubinLonger durationCycle 1Patients
2018
Safety and pharmacokinetics of MM-302, a HER2-targeted antibody–liposomal doxorubicin conjugate, in patients with advanced HER2-positive breast cancer: a phase 1 dose-escalation study
Munster P, Krop IE, LoRusso P, Ma C, Siegel BA, Shields AF, Molnár I, Wickham TJ, Reynolds J, Campbell K, Hendriks BS, Adiwijaya BS, Geretti E, Moyo V, Miller KD. Safety and pharmacokinetics of MM-302, a HER2-targeted antibody–liposomal doxorubicin conjugate, in patients with advanced HER2-positive breast cancer: a phase 1 dose-escalation study. British Journal Of Cancer 2018, 119: 1086-1093. PMID: 30361524, PMCID: PMC6219487, DOI: 10.1038/s41416-018-0235-2.Peer-Reviewed Original ResearchConceptsOverall response rateAdverse eventsMM-302Breast cancerAdvanced HER2-positive breast cancerPhase 1 dose-escalation studyPhase 1 dose-escalation trialGrade 3/4 adverse eventsHER2-positive breast cancerAnthracycline-naïve patientsResultsSixty-nine patientsCommon adverse eventsDose-escalation studyDose-escalation trialPalmar-plantar erythrodysesthesiaMetastatic breast cancerFebrile neutropeniaMucosal inflammationPromising efficacyResponse rateTrastuzumabQ3wPatientsMonotherapyNeutropeniaA phase II study of atezolizumab (Atezo) combined with pertuzumab (P) and high-dose trastuzumab (H) for the treatment of central nervous system (CNS) metastases in patients with Her2-positive (HER2+) metastatic breast cancer (MBC).
Barroso-Sousa R, Barry W, Kumthekar P, Guo H, Silvestri K, Krop I, Winer E, Tolaney S, Lin N. A phase II study of atezolizumab (Atezo) combined with pertuzumab (P) and high-dose trastuzumab (H) for the treatment of central nervous system (CNS) metastases in patients with Her2-positive (HER2+) metastatic breast cancer (MBC). Journal Of Clinical Oncology 2018, 36: tps1100-tps1100. DOI: 10.1200/jco.2018.36.15_suppl.tps1100.Peer-Reviewed Original ResearchHER2-enriched subtype and ERBB2 mRNA as predictors of pathological complete response following trastuzumab and lapatinib without chemotherapy in early-stage HER2-positive breast cancer: A combined analysis of TBCRC006/023 and PAMELA trials.
Prat A, De Angelis C, Pascual T, Gutierrez C, Llombart-Cussac A, Wang T, Cortes J, Rexer B, Veeraraghavan J, Forero-Torres A, Wolff A, Morales S, Krop I, Pavlick A, Bermejo B, Hilsenbeck S, Oliveira M, Schiff R, Osborne C, Rimawi M. HER2-enriched subtype and ERBB2 mRNA as predictors of pathological complete response following trastuzumab and lapatinib without chemotherapy in early-stage HER2-positive breast cancer: A combined analysis of TBCRC006/023 and PAMELA trials. Journal Of Clinical Oncology 2018, 36: 509-509. DOI: 10.1200/jco.2018.36.15_suppl.509.Peer-Reviewed Original Research
2017
Low PTEN levels and PIK3CA mutations predict resistance to neoadjuvant lapatinib and trastuzumab without chemotherapy in patients with HER2 over-expressing breast cancer
Rimawi MF, De Angelis C, Contreras A, Pareja F, Geyer FC, Burke KA, Herrera S, Wang T, Mayer IA, Forero A, Nanda R, Goetz MP, Chang JC, Krop IE, Wolff AC, Pavlick AC, Fuqua SAW, Gutierrez C, Hilsenbeck SG, Li MM, Weigelt B, Reis-Filho JS, Kent Osborne C, Schiff R. Low PTEN levels and PIK3CA mutations predict resistance to neoadjuvant lapatinib and trastuzumab without chemotherapy in patients with HER2 over-expressing breast cancer. Breast Cancer Research And Treatment 2017, 167: 731-740. PMID: 29110152, PMCID: PMC5821069, DOI: 10.1007/s10549-017-4533-9.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsClass I Phosphatidylinositol 3-KinasesFemaleGene Expression Regulation, NeoplasticHumansLapatinibMiddle AgedMutationNeoadjuvant TherapyPTEN PhosphohydrolaseQuinazolinesReceptor, ErbB-2TrastuzumabConceptsPathologic complete responsePIK3CA mutationsBreast cancerPTEN expression levelsPTEN statusClinical trialsHER2-positive breast cancerNeoadjuvant clinical trialsPIK3CA mutation analysisLow PTEN expression levelsExpression levelsPI3K pathwayEvaluable patientsNeoadjuvant lapatinibComplete responsePatientsChemotherapyPTEN immunohistochemistryTumor samplesTrastuzumabCancerPathway activationK pathwayFurther studiesPTEN levels
2016
315TiP HERMIONE: A phase 2, randomized, open label trial comparing MM-302 plus trastuzumab with chemotherapy of physician's choice plus trastuzumab, in anthracycline naive HER2-positive, locally advanced/metastatic breast cancer patients previously treated with pertuzumab and T-DM1
Castan J, Verma S, Hurvitz S, Krop I, Tripathy D, Yardley D, Dionne M, Reynolds J, Wickham T, Molnar I, Miller K. 315TiP HERMIONE: A phase 2, randomized, open label trial comparing MM-302 plus trastuzumab with chemotherapy of physician's choice plus trastuzumab, in anthracycline naive HER2-positive, locally advanced/metastatic breast cancer patients previously treated with pertuzumab and T-DM1. Annals Of Oncology 2016, 27: vi99. DOI: 10.1093/annonc/mdw365.94.Peer-Reviewed Original ResearchHERMIONE: A Phase 2, randomized, open label trial comparing MM-302 plus trastuzumab with chemotherapy of physician’s choice plus trastuzumab, in anthracycline naive HER2-positive, locally advanced/metastatic breast cancer patients previously treated with pertuzumab and ado-trastuzumab emtansine (T-DM1).
Miller K, Cortes J, Hurvitz S, Krop I, Tripathy D, Verma S, Dionne M, Campbell K, Reynolds J, Wickham T, Molnar I, Yardley D. HERMIONE: A Phase 2, randomized, open label trial comparing MM-302 plus trastuzumab with chemotherapy of physician’s choice plus trastuzumab, in anthracycline naive HER2-positive, locally advanced/metastatic breast cancer patients previously treated with pertuzumab and ado-trastuzumab emtansine (T-DM1). Journal Of Clinical Oncology 2016, 34: tps631-tps631. DOI: 10.1200/jco.2016.34.15_suppl.tps631.Peer-Reviewed Original Research
2015
HERMIONE: A Phase 2, randomized, open label trial comparing MM-302 plus trastuzumab with chemotherapy of physician’s choice plus trastuzumab, in anthracycline naive HER2-positive, locally advanced/metastatic breast cancer patients previously treated with pertuzumab and ado-trastuzumab emtansine (T-DM1).
Miller K, Cortes J, Hurvitz S, Krop I, Tripathy D, Verma S, Riahi K, Reynolds J, Wickham T, Molnar I, Yardley D. HERMIONE: A Phase 2, randomized, open label trial comparing MM-302 plus trastuzumab with chemotherapy of physician’s choice plus trastuzumab, in anthracycline naive HER2-positive, locally advanced/metastatic breast cancer patients previously treated with pertuzumab and ado-trastuzumab emtansine (T-DM1). Journal Of Clinical Oncology 2015, 33: tps641-tps641. DOI: 10.1200/jco.2015.33.15_suppl.tps641.Peer-Reviewed Original ResearchWhole exome sequencing (WES) in HER2+ metastatic breast cancer (MBC) patients (pts) with extraordinary responses to trastuzumab (T).
Luis I, Oh C, Wang Z, Dipiro P, Macrae E, Painter C, Kryukov G, Krop I, Winer E, Lin N, Wagle N. Whole exome sequencing (WES) in HER2+ metastatic breast cancer (MBC) patients (pts) with extraordinary responses to trastuzumab (T). Journal Of Clinical Oncology 2015, 33: 611-611. DOI: 10.1200/jco.2015.33.15_suppl.611.Peer-Reviewed Original ResearchChemotherapy-related amenorrhea after adjuvant paclitaxel–trastuzumab (APT trial)
Ruddy KJ, Guo H, Barry W, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis MJ, Shapira I, Wolff AC, Carey LA, Overmoyer BA, Hudis C, Krop IE, Burstein HJ, Winer EP, Partridge AH, Tolaney SM. Chemotherapy-related amenorrhea after adjuvant paclitaxel–trastuzumab (APT trial). Breast Cancer Research And Treatment 2015, 151: 589-596. PMID: 25981899, PMCID: PMC5057177, DOI: 10.1007/s10549-015-3426-z.Peer-Reviewed Original ResearchConceptsChemotherapy-related amenorrheaChemotherapy initiationMenopausal symptomsBreast cancerAdjuvant breast cancer therapyEarly-stage breast cancerNode-negative HER2Weeks of paclitaxelStage breast cancerLast menstrual periodBreast cancer therapyAdjuvant paclitaxelAmenorrhea ratesAPT trialEligible patientsEvaluable populationPremenopausal womenAdjuvant studiesTrastuzumab monotherapyMedian timeMenstrual periodCancer regimensAmenorrheaTrastuzumabMonths
2014
Gene expression signatures in pre- and post-therapy (Rx) specimens from CALGB 40601 (Alliance), a neoadjuvant phase III trial of weekly paclitaxel and trastuzumab with or without lapatinib for HER2-positive breast cancer (BrCa).
Carey L, Barry W, Pitcher B, Hoadley K, Cheang M, Anders C, Henry N, Tolaney S, Dang C, Krop I, Harris L, Berry D, Perou C, Winer E, Hudis C. Gene expression signatures in pre- and post-therapy (Rx) specimens from CALGB 40601 (Alliance), a neoadjuvant phase III trial of weekly paclitaxel and trastuzumab with or without lapatinib for HER2-positive breast cancer (BrCa). Journal Of Clinical Oncology 2014, 32: 506-506. DOI: 10.1200/jco.2014.32.15_suppl.506.Peer-Reviewed Original ResearchA phase II study of eribulin mesylate in combination with trastuzumab and pertuzumab in patients (pts) with metastatic, human epidermal growth factor receptor 2-positive breast cancer.
Freedman R, Luis I, Barry W, Krop I, Wagle N, Lowe A, Galler S, Sohl J, Isakoff S, Tung N, Winer E, Lin N. A phase II study of eribulin mesylate in combination with trastuzumab and pertuzumab in patients (pts) with metastatic, human epidermal growth factor receptor 2-positive breast cancer. Journal Of Clinical Oncology 2014, 32: tps668-tps668. DOI: 10.1200/jco.2014.32.15_suppl.tps668.Peer-Reviewed Original ResearchWhole-exome sequencing (WES) of HER2+ metastatic breast cancer (MBC) from patients (pts) treated with prior trastuzumab (T): A correlative analysis of TBCRC003.
Wagle N, Lin N, Richardson A, Leshchiner I, Mayer I, Forero-Torres A, Hobday T, Dees E, Nanda R, Rimawi M, Guo H, Barry W, Wolff A, Gabriel S, Garraway L, Winer E, Krop I. Whole-exome sequencing (WES) of HER2+ metastatic breast cancer (MBC) from patients (pts) treated with prior trastuzumab (T): A correlative analysis of TBCRC003. Journal Of Clinical Oncology 2014, 32: 536-536. DOI: 10.1200/jco.2014.32.15_suppl.536.Peer-Reviewed Original ResearchPhase I dose-escalation trial of ONT-380 in combination with trastuzumab in participants with brain metastases from HER2+ breast cancer.
Metzger-Filho O, Barry W, Krop I, Younger W, Lawler E, Winer E, Lin N. Phase I dose-escalation trial of ONT-380 in combination with trastuzumab in participants with brain metastases from HER2+ breast cancer. Journal Of Clinical Oncology 2014, 32: tps660-tps660. DOI: 10.1200/jco.2014.32.15_suppl.tps660.Peer-Reviewed Original ResearchRelationship between tumor biomarkers (BM) and efficacy in TH3RESA, a phase 3 study of trastuzumab emtansine (T-DM1) versus treatment of physician’s choice (TPC) in HER2-positive advanced breast cancer (BC) previously treated with trastuzumab and lapatinib.
Kim S, Wildiers H, Krop I, Leung A, Trudeau C, Yu R, de Haas S, Gonzalez-Martin A. Relationship between tumor biomarkers (BM) and efficacy in TH3RESA, a phase 3 study of trastuzumab emtansine (T-DM1) versus treatment of physician’s choice (TPC) in HER2-positive advanced breast cancer (BC) previously treated with trastuzumab and lapatinib. Journal Of Clinical Oncology 2014, 32: 605-605. DOI: 10.1200/jco.2014.32.15_suppl.605.Peer-Reviewed Original Research