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
2023
A Multiparameter Molecular Classifier to Predict Response to Neoadjuvant Lapatinib plus Trastuzumab without Chemotherapy in HER2+ Breast Cancer.
Veeraraghavan J, Gutierrez C, De Angelis C, Davis R, Wang T, Pascual T, Selenica P, Sanchez K, Nitta H, Kapadia M, Pavlick A, Galvan P, Rexer B, Forero-Torres A, Nanda R, Storniolo A, Krop I, Goetz M, Nangia J, Wolff A, Weigelt B, Reis-Filho J, Hilsenbeck S, Prat A, Osborne C, Schiff R, Rimawi M. A Multiparameter Molecular Classifier to Predict Response to Neoadjuvant Lapatinib plus Trastuzumab without Chemotherapy in HER2+ Breast Cancer. Clinical Cancer Research 2023, 29: 3101-3109. PMID: 37195235, PMCID: PMC10923553, DOI: 10.1158/1078-0432.ccr-22-3753.Peer-Reviewed Original ResearchAnti-HER2 therapyBreast cancerDual anti-HER2 therapyPathologic complete response rateEstrogen receptor-positive tumorsPIK3CA mutation statusComplete response rateReceptor-positive tumorsBreast cancer specimensHigh NPVNegative predictive valueEndocrine therapyNeoadjuvant lapatinibNeoadjuvant treatmentTreatment deescalationUnselected patientsClinical trialsCancer specimensMutation statusPatientsPredictive valueResponse rateChemotherapyHER2HER2 protein
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 Research120MO Prognostic value of immune gene-expression signatures (iGES) vs tumor-infiltrating lymphocytes (TILs) in early-stage HER2+ breast cancer: A combined analysis of CALGB 40601 (C40601) and PAMELA trials
Fernandez-Martinez A, Pascual T, Singh B, Nuciforo P, Hoadley K, Rashid N, Spears P, Chic N, Krop I, Hillman D, Partridge A, Prat A, Carey L, Perou C. 120MO Prognostic value of immune gene-expression signatures (iGES) vs tumor-infiltrating lymphocytes (TILs) in early-stage HER2+ breast cancer: A combined analysis of CALGB 40601 (C40601) and PAMELA trials. Annals Of Oncology 2021, 32: s409. DOI: 10.1016/j.annonc.2021.08.401.Peer-Reviewed Original ResearchFOXA1 and adaptive response determinants to HER2 targeted therapy in TBCRC 036
Angus SP, Stuhlmiller TJ, Mehta G, Bevill SM, Goulet DR, Olivares-Quintero JF, East MP, Tanioka M, Zawistowski JS, Singh D, Sciaky N, Chen X, He X, Rashid NU, Chollet-Hinton L, Fan C, Soloway MG, Spears PA, Jefferys S, Parker JS, Gallagher KK, Forero-Torres A, Krop IE, Thompson AM, Murthy R, Gatza ML, Perou CM, Earp HS, Carey LA, Johnson GL. FOXA1 and adaptive response determinants to HER2 targeted therapy in TBCRC 036. Npj Breast Cancer 2021, 7: 51. PMID: 33980863, PMCID: PMC8115531, DOI: 10.1038/s41523-021-00258-0.Peer-Reviewed Original ResearchHER2/ErbB2 receptorGene signatureAnti-HER2 monoclonal antibodyHER2-positive malignanciesImmune gene signaturesAnti-HER2 therapyHER2-positive breastPotential therapeutic strategyAnti-HER2 antibodyFOXA1 depletionHER3 levelsProliferation gene signatureClinical trialsPharmacodynamic responseBreast cancerImmune responseTherapeutic strategiesFOXA1 expressionTranscription factor FOXA1Cell line responseHER2Adaptive responseMonoclonal antibodiesAdaptive upregulationLapatinib128TiP 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 multiparameter classifier to predict response to lapatinib plus trastuzumab (LT) without chemotherapy in HER2+ breast cancer (BC).
Veeraraghavan J, Gutierrez C, De Angelis C, Wang T, Pascual T, Weigelt B, Galvan P, Rexer B, Forero-Torres A, Wolff A, Nanda R, Storniolo A, Krop I, Goetz M, Reis-Filho J, Hilsenbeck S, Prat A, Osborne C, Schiff R, Rimawi M. A multiparameter classifier to predict response to lapatinib plus trastuzumab (LT) without chemotherapy in HER2+ breast cancer (BC). Journal Of Clinical Oncology 2020, 38: 1011-1011. DOI: 10.1200/jco.2020.38.15_suppl.1011.Peer-Reviewed Original ResearchPIK3CA mutation statusBreast cancerHER2 ratioMutation statusPathologic complete response rateIntratumor heterogeneityRate of CTXComplete response rateData cohortDe-escalation strategiesLT therapyEvaluable patientsUnselected patientsClinical trialsTargeted therapyProspective validationHER2 geneResponse rateAdditional casesHER2PatientsHER2 proteinCohortPAM50Protein levelsManagement 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
2019
A combinatorial biomarker predicts pathologic complete response to neoadjuvant lapatinib and trastuzumab without chemotherapy in patients with HER2+ breast cancer
Veeraraghavan J, De Angelis C, Mao R, Wang T, Herrera S, Pavlick AC, Contreras A, Nuciforo P, Mayer IA, Forero A, Nanda R, Goetz MP, Chang JC, Wolff AC, Krop IE, Fuqua SAW, Prat A, Hilsenbeck SG, Weigelt B, Reis-Filho JS, Gutierrez C, Osborne CK, Rimawi MF, Schiff R. A combinatorial biomarker predicts pathologic complete response to neoadjuvant lapatinib and trastuzumab without chemotherapy in patients with HER2+ breast cancer. Annals Of Oncology 2019, 30: 927-933. PMID: 30903140, PMCID: PMC6594453, DOI: 10.1093/annonc/mdz076.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsClass I Phosphatidylinositol 3-KinasesFemaleFollow-Up StudiesGene AmplificationHumansIn Situ Hybridization, FluorescenceLapatinibNeoadjuvant TherapyPhosphatidylinositol 3-KinasesPrognosisReceptor, ErbB-2Remission InductionTrastuzumabConceptsPathologic complete responsePI3K pathway statusBreast cancerHER2 ratioPI3K pathwayNeoadjuvant lapatinibComplete responseHER2 amplificationPathway statusHER2-positive breast cancerPI3K pathway alterationsHER2 amplification levelHER2 FISH ratioK pathwayAnti-HER2 therapyWild-type PIK3CAPI3K pathway activationPIK3CA mutationsClinical subtypesHER2 overexpressionFISH ratioPatientsChemotherapyHER2High PTEN197TiP Phase III study of [fam-] trastuzumab deruxtecan vs investigator’s choice in T-DM1-pretreated HER2+ breast cancer
André F, Shahidi J, Lee C, Wang K, Krop I. 197TiP Phase III study of [fam-] trastuzumab deruxtecan vs investigator’s choice in T-DM1-pretreated HER2+ breast cancer. Annals Of Oncology 2019, 30: iii63. DOI: 10.1093/annonc/mdz100.048.Peer-Reviewed Original Research
2018
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.
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
264P Progression-free survival (PFS) and site of first progression in HER2+ metastatic breast cancer (MBC) patients (pts) with (w) or without (w/o) brain metastases: A pooled analysis of tucatinib phase I studies
Moulder S, Hamilton E, Ferrario C, Conlin A, Krop I, Chamberlain M, Gray T, Borges V. 264P Progression-free survival (PFS) and site of first progression in HER2+ metastatic breast cancer (MBC) patients (pts) with (w) or without (w/o) brain metastases: A pooled analysis of tucatinib phase I studies. Annals Of Oncology 2017, 28: v85. DOI: 10.1093/annonc/mdx365.027.Peer-Reviewed Original ResearchTBCRC 036: Window of opportunity clinical trial reveals adaptive kinome reprogramming in single and combination HER2-targeting in breast cancer (BrCa).
Angus S, Stuhlmiller T, Sciaky N, Chen X, Naim R, Tanioka M, Gallagher K, Forero A, Krop I, Thompson A, Murthy R, He X, Perou C, Earp S, Carey L, Johnson G. TBCRC 036: Window of opportunity clinical trial reveals adaptive kinome reprogramming in single and combination HER2-targeting in breast cancer (BrCa). Journal Of Clinical Oncology 2017, 35: 1027-1027. DOI: 10.1200/jco.2017.35.15_suppl.1027.Peer-Reviewed Original ResearchHER2 targetingOpportunity clinical trialAnti-HER2 drugsKinome reprogrammingKinase-targeted therapiesEligible patientsEvaluable ptsTyrosine kinaseImmune compartmentBreast surgeryHER2 inhibitionMultiplexed Inhibitor BeadsClinical trialsBreast cancerImmune responseSpecific receptor tyrosine kinasesBrCa cellsReceptor tyrosine kinasesTumor cellsKinome responsesHER2Distinct expressionKinase SykResistance mechanismsRNA sequencing
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 Research313TiP SANDPIPER: Phase III study of the PI3-kinase (PI3K) inhibitor taselisib (GDC-0032) plus fulvestrant in patients (pts) with oestrogen receptor (ER)-positive, HER2-negative locally advanced or metastatic breast cancer (BC) enriched for pts with PIK3CA-mutant tumours
Baselga J, Castan J, De Laurentiis M, Dieras V, Harbeck N, Hsu J, Jin H, Schimmoller F, Wilson T, Im Y, Jacot W, Krop I, Verma S. 313TiP SANDPIPER: Phase III study of the PI3-kinase (PI3K) inhibitor taselisib (GDC-0032) plus fulvestrant in patients (pts) with oestrogen receptor (ER)-positive, HER2-negative locally advanced or metastatic breast cancer (BC) enriched for pts with PIK3CA-mutant tumours. Annals Of Oncology 2016, 27: vi99. DOI: 10.1093/annonc/mdw365.92.Peer-Reviewed Original Research1560P Quantitative evaluation of HER2-mediated cellular uptake of the HER2-targeted antibody-liposomal doxorubicin conjugate MM-302 suggests potential for treating HER2-intermediate tumors
Geretti E, Espelin C, Adiwijaya B, Dumont N, Coma S, Koncki Z, Garcia G, Bloom T, Rimkunas V, Reynolds J, Campbell K, Moyo V, Molnar I, Lorusso P, Miller K, Ma C, Krop I, Munster P, Wickham T. 1560P Quantitative evaluation of HER2-mediated cellular uptake of the HER2-targeted antibody-liposomal doxorubicin conjugate MM-302 suggests potential for treating HER2-intermediate tumors. Annals Of Oncology 2016, 27: vi539. DOI: 10.1093/annonc/mdw392.41.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 ResearchA phase II study of the PI3K inhibitor taselisib (GDC-0032) combined with fulvestrant (F) in patients (pts) with HER2-negative (HER2-), hormone receptor-positive (HR+) advanced breast cancer (BC).
Dickler M, Saura C, Richards D, Krop I, Cervantes A, Bedard P, Patel M, Pusztai L, Oliveira M, Ware J, Jin H, Wilson T, Stout T, Wei M, Hsu J, Baselga J. A phase II study of the PI3K inhibitor taselisib (GDC-0032) combined with fulvestrant (F) in patients (pts) with HER2-negative (HER2-), hormone receptor-positive (HR+) advanced breast cancer (BC). Journal Of Clinical Oncology 2016, 34: 520-520. DOI: 10.1200/jco.2016.34.15_suppl.520.Peer-Reviewed Original ResearchEfficacy results of a phase 1b study of ONT-380, a CNS-penetrant TKI, in combination with T-DM1 in HER2+ metastatic breast cancer (MBC), including patients (pts) with brain metastases.
Borges V, Ferrario C, Aucoin N, Falkson C, Khan Q, Krop I, Welch S, Bedard P, Conlin A, Chaves J, Walker L, Hamilton E. Efficacy results of a phase 1b study of ONT-380, a CNS-penetrant TKI, in combination with T-DM1 in HER2+ metastatic breast cancer (MBC), including patients (pts) with brain metastases. Journal Of Clinical Oncology 2016, 34: 513-513. DOI: 10.1200/jco.2016.34.15_suppl.513.Peer-Reviewed Original ResearchSANDPIPER: 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, Cortes J, De Laurentiis M, Dieras V, Harbeck N, Hsu J, Ng V, 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 2016, 34: tps617-tps617. DOI: 10.1200/jco.2016.34.15_suppl.tps617.Peer-Reviewed Original Research