2024
Neratinib and Ado-Trastuzumab-Emtansine for Pre-treated and Untreated HER2-positive Breast Cancer Brain Metastases: Translational Breast Cancer Research Consortium Trial 022
Freedman R, Heiling H, Li T, Trapani D, Tayob N, Smith K, Davis R, Pereslete A, DeMeo M, Cotter C, Chen W, Parsons H, Santa-Maria C, Van Poznak C, Moy B, Brufsky A, Melisko M, O’Sullivan C, Ashai N, Rauf Y, Nangia J, Burns R, Savoie J, Wolff A, Winer E, Rimawi M, Krop I, Lin N. Neratinib and Ado-Trastuzumab-Emtansine for Pre-treated and Untreated HER2-positive Breast Cancer Brain Metastases: Translational Breast Cancer Research Consortium Trial 022. Annals Of Oncology 2024 PMID: 38977064, DOI: 10.1016/j.annonc.2024.07.245.Peer-Reviewed Original ResearchHER2-positive breast cancer brain metastasesBreast cancer brain metastasesT-DM1Ado-trastuzumab emtansineCentral nervous systemOverall survivalCNS objective response rateEfficacy of neratinibT-DM1 exposureObjective response rateCancer brain metastasesPhase II studyMedian OSRANO-BMBrain MetastasesSlow accrualIntracranial activityII studyPrimary endpointPreclinical dataCohort 4Response assessmentTreatment optionsNeratinibPatients182MO 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
377O A pooled analysis of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-positive (HER2+) metastatic breast cancer (mBC) with brain metastases (BMs) from DESTINY-Breast (DB) -01, -02, and -03
Hurvitz S, Modi S, Li W, Park Y, Chung W, Kim S, Cortés J, Yamashita T, Pedrini J, Im S, Tseng L, Harbeck N, Krop I, Curigliano G, Mathias E, Cathcart J, Cagnazzo A, Ashfaque S, Egorov A, André F. 377O A pooled analysis of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-positive (HER2+) metastatic breast cancer (mBC) with brain metastases (BMs) from DESTINY-Breast (DB) -01, -02, and -03. Annals Of Oncology 2023, 34: s335-s336. DOI: 10.1016/j.annonc.2023.09.554.Peer-Reviewed Original ResearchCirculating tumor DNA association with residual cancer burden after neoadjuvant chemotherapy in triple-negative breast cancer in TBCRC 030 ☆
Parsons H, Blewett T, Chu X, Sridhar S, Santos K, Xiong K, Abramson V, Patel A, Cheng J, Brufsky A, Rhoades J, Force J, Liu R, Traina T, Carey L, Rimawi M, Miller K, Stearns V, Specht J, Falkson C, Burstein H, Wolff A, Winer E, Tayob N, Krop I, Makrigiorgos G, Golub T, Mayer E, Adalsteinsson V. Circulating tumor DNA association with residual cancer burden after neoadjuvant chemotherapy in triple-negative breast cancer in TBCRC 030 ☆. Annals Of Oncology 2023, 34: 899-906. PMID: 37597579, PMCID: PMC10898256, DOI: 10.1016/j.annonc.2023.08.004.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerResidual cancer burdenNeoadjuvant chemotherapyCancer burdenBreast cancerWeek 3Additional neoadjuvant chemotherapyPlasma samplesCase-control analysisCtDNA clearanceCtDNA positivityNeoadjuvant paclitaxelDisease recurrenceProspective studyWeek 12RCB 0CtDNA assaysPatientsSufficient tissueChemotherapyTumor fractionTumor DNARCB-3RespondersAdditional studiesGenomics of ERBB2-Positive Breast Cancer in Young Women Before and After Exposure to Chemotherapy Plus Trastuzumab.
Lipsyc-Sharf M, Jain E, Collins L, Rosenberg S, Ruddy K, Tamimi R, Schapira L, Come S, Peppercorn J, Borges V, Warner E, Snow C, Krop I, Kim D, Weiss J, Zanudo J, Partridge A, Wagle N, Waks A. Genomics of ERBB2-Positive Breast Cancer in Young Women Before and After Exposure to Chemotherapy Plus Trastuzumab. JCO Precision Oncology 2023, 7: e2300076. PMID: 37364233, DOI: 10.1200/po.23.00076.Peer-Reviewed Original ResearchConceptsPositive breast cancerWhole-exome sequencingBreast cancerYoung womenWomen age 40 yearsErbB2-positive breast cancerErb-b2 receptor tyrosine kinase 2Half of patientsTime pointsLarge prospective cohortAge 40 yearsPost-treatment tumorsReceptor tyrosine kinase 2Post-treatment specimensPost-treatment samplesProspective cohortPositive tumorsTyrosine kinase 2Cancer-related genesPatientsTumor-normal pairsTherapeutic resistanceTumor tissueCNS changesHotspot mutationsA 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 protein186O Patient-reported outcomes (PROs) from DESTINY-Breast02, a randomized phase III study of trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice (TPC) in patients (pts) with HER2–positive (HER2+) metastatic breast cancer (mBC)
Fehm T, Cottone F, Dunton K, André F, Krop I, Park Y, De Laurentiis M, Miyoshi Y, Armstrong A, Borrego M, Yerushalmi R, Duhoux F, Takano T, Lu W, Livings C, Egorov A, Kim S. 186O Patient-reported outcomes (PROs) from DESTINY-Breast02, a randomized phase III study of trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice (TPC) in patients (pts) with HER2–positive (HER2+) metastatic breast cancer (mBC). ESMO Open 2023, 8: 101375. DOI: 10.1016/j.esmoop.2023.101375.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 Research175P Alpelisib (ALP) + endocrine therapy (ET) in patients (pts) with PIK3CA-mutated, hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC): Subgroup analyses from the BYLieve study
Cardoso F, Juric D, Lerebours F, Krop I, Borrego M, Neven P, Park Y, Yardley D, Jhaveri K, Arce C, Gu E, Akdere M, Rugo H. 175P Alpelisib (ALP) + endocrine therapy (ET) in patients (pts) with PIK3CA-mutated, hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC): Subgroup analyses from the BYLieve study. Annals Of Oncology 2022, 33: s206-s207. DOI: 10.1016/j.annonc.2022.03.194.Peer-Reviewed Original ResearchSix-year absolute invasive disease-free survival benefit of adding adjuvant pertuzumab to trastuzumab and chemotherapy for patients with early HER2-positive breast cancer: A Subpopulation Treatment Effect Pattern Plot (STEPP) analysis of the APHINITY (BIG 4-11) trial
Gelber RD, Wang XV, Cole BF, Cameron D, Cardoso F, Tjan-Heijnen V, Krop I, Loi S, Salgado R, Kiermaier A, Frank E, Fumagalli D, Caballero C, de Azambuja E, Procter M, Clark E, Restuccia E, Heeson S, Bines J, Loibl S, Piccart-Gebhart M, Committee and Investigators A. Six-year absolute invasive disease-free survival benefit of adding adjuvant pertuzumab to trastuzumab and chemotherapy for patients with early HER2-positive breast cancer: A Subpopulation Treatment Effect Pattern Plot (STEPP) analysis of the APHINITY (BIG 4-11) trial. European Journal Of Cancer 2022, 166: 219-228. PMID: 35313167, DOI: 10.1016/j.ejca.2022.01.031.Peer-Reviewed Original ResearchConceptsSubpopulation treatment effect pattern plotInvasive disease-free survivalComposite risk scoreAdjuvant pertuzumabAPHINITY trialTIL percentageBreast cancerRisk scoreSubpopulation treatment effect pattern plot analysisEarly HER2-positive breast cancerDisease-free survival benefitHER2-positive breast cancerTreatment effectsNode-positive cohortDisease-free survivalEarly breast cancerNodal statusSurvival benefitLymphocyte percentagePatient subpopulationsComposite riskPatientsCovariates of interestChemotherapyPertuzumab
2021
279P 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 Research331TiP 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 ResearchAdjuvant 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 toxicityWeeksTrastuzumabCancerPaclitaxelA phase I/Ib study evaluating GDC-0077 (inavolisib) + palbociclib (palbo) + fulvestrant in patients (pts) with PIK3CA-mutant (mut), hormone receptor-positive/HER2-negative metastatic breast cancer (HR+/HER2- mBC)
Schmid P, Bedard P, Jhaveri K, Cervantes A, Gambardella V, Hamilton E, Italiano A, Kalinsky K, Krop I, Oliveira M, Saura C, Turner N, Varga A, Hutchinson K, Lei G, Royer-Joo S, Thomas P, JL S, Juric D. A phase I/Ib study evaluating GDC-0077 (inavolisib) + palbociclib (palbo) + fulvestrant in patients (pts) with PIK3CA-mutant (mut), hormone receptor-positive/HER2-negative metastatic breast cancer (HR+/HER2- mBC). Senologie - Zeitschrift Für Mammadiagnostik Und -therapie 2021, 18: e36-e37. DOI: 10.1055/s-0041-1730220.Peer-Reviewed Original ResearchPharmacokinetic (PK) analyses in CSF and plasma from TBCRC049, an ongoing trial to assess the safety and efficacy of the combination of tucatinib, trastuzumab and capecitabine for the treatment of leptomeningeal metastasis (LM) in HER2 positive breast cancer.
Stringer-Reasor E, O'Brien B, Topletz-Erickson A, White J, Lobbous M, Riley K, Childress J, LaMaster K, Melisko M, Morikawa A, De Groot J, Krop I, Valero V, Rimawi M, Wolff A, Tripathy D, Lin N, Murthy R. Pharmacokinetic (PK) analyses in CSF and plasma from TBCRC049, an ongoing trial to assess the safety and efficacy of the combination of tucatinib, trastuzumab and capecitabine for the treatment of leptomeningeal metastasis (LM) in HER2 positive breast cancer. Journal Of Clinical Oncology 2021, 39: 1044-1044. DOI: 10.1200/jco.2021.39.15_suppl.1044.Peer-Reviewed Original ResearchLeptomeningeal metastasesBrain metastasesBreast cancerPharmacokinetic analysisPhase 2 single-arm studyHER2-positive breast cancerCombination of tucatinibNew brain metastasesSingle-arm studyPositive breast cancerTyrosine kinase inhibitorsHigh interindividual variabilityMetastatic HER2Accrual goalEligible patientsMetastatic settingPrimary endpointOverall survivalOmmaya reservoirOngoing trialsPlasma concentrationsCapecitabinePatientsDay 1PK samples128TiP 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 ResearchGenomic Characterization of de novo Metastatic Breast Cancer
Garrido-Castro AC, Spurr LF, Hughes ME, Li YY, Cherniack AD, Kumari P, Lloyd MR, Bychkovsky B, Barroso-Sousa R, Di Lascio S, Jain E, Files J, Mohammed-Abreu A, Krevalin M, MacKichan C, Barry WT, Guo H, Xia D, Cerami E, Rollins BJ, MacConaill LE, Lindeman NI, Krop IE, Johnson BE, Wagle N, Winer EP, Dillon DA, Lin NU. Genomic Characterization of de novo Metastatic Breast Cancer. Clinical Cancer Research 2021, 27: 1105-1118. PMID: 33293374, PMCID: PMC7887078, DOI: 10.1158/1078-0432.ccr-20-1720.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerPrimary tumorOverall survivalBreast cancerDe novo metastatic breast cancerNovo metastatic breast cancerDifferential therapeutic sensitivityBetter OSPoor OSShorter OSInitial diagnosisHigh TMBMetastatic tumorsDnMBCCurrent treatmentMutational burdenTreatment selectionMetastatic driversStage IMultiple comparison adjustmentTherapeutic sensitivityTumorsPatientsCancerIntrinsic resistance
2020
Publisher Correction: Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis
Brastianos PK, Lee EQ, Cohen JV, Tolaney SM, Lin NU, Wang N, Chukwueke U, White MD, Nayyar N, Kim A, Alvarez-Breckenridge C, Krop I, Mahar MK, Bertalan MS, Shaw B, Mora JL, Goss N, Subramanian M, Nayak L, Dietrich J, Forst DA, Nahed BV, Batchelor TT, Shih HA, Gerstner ER, Moy B, Lawrence D, Giobbie-Hurder A, Carter SL, Oh K, Cahill DP, Sullivan RJ. Publisher Correction: Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis. Nature Medicine 2020, 26: 1309-1309. PMID: 32555425, DOI: 10.1038/s41591-020-0978-1.Peer-Reviewed Original ResearchSingle-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis
Brastianos PK, Lee EQ, Cohen JV, Tolaney SM, Lin NU, Wang N, Chukwueke U, White MD, Nayyar N, Kim A, Alvarez-Breckenridge C, Krop I, Mahar MK, Bertalan MS, Shaw B, Mora JL, Goss N, Subramanian M, Nayak L, Dietrich J, Forst DA, Nahed BV, Batchelor TT, Shih HA, Gerstner ER, Moy B, Lawrence D, Giobbie-Hurder A, Carter SL, Oh K, Cahill DP, Sullivan RJ. Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis. Nature Medicine 2020, 26: 1280-1284. PMID: 32483359, DOI: 10.1038/s41591-020-0918-0.Peer-Reviewed Original ResearchConceptsPrimary endpointOpen-label phase 2 trialDose of pembrolizumabExtracranial disease progressionHigher adverse eventsPercentage of patientsPhase 2 studyPhase 2 trialSolid tumor malignanciesFraction of patientsDefinitive progressionUnacceptable toxicityAdverse eventsOverall survivalPatients 17Leptomeningeal carcinomatosisLeptomeningeal disseminationLung cancerDisease progressionOvarian cancerMetastatic cancerPembrolizumabBreast cancerGrade 3PatientsSensitive Detection of Minimal Residual Disease in Patients Treated for Early-Stage Breast Cancer
Parsons HA, Rhoades J, Reed SC, Gydush G, Ram P, Exman P, Xiong K, Lo CC, Li T, Fleharty M, Kirkner GJ, Rotem D, Cohen O, Yu F, Fitarelli-Kiehl M, Leong KW, Hughes ME, Rosenberg SM, Collins LC, Miller KD, Blumenstiel B, Trippa L, Cibulskis C, Neuberg DS, DeFelice M, Freeman SS, Lennon NJ, Wagle N, Ha G, Stover DG, Choudhury AD, Getz G, Winer EP, Meyerson M, Lin NU, Krop I, Love JC, Makrigiorgos GM, Partridge AH, Mayer EL, Golub TR, Adalsteinsson VA. Sensitive Detection of Minimal Residual Disease in Patients Treated for Early-Stage Breast Cancer. Clinical Cancer Research 2020, 26: 2556-2564. PMID: 32170028, PMCID: PMC7654718, DOI: 10.1158/1078-0432.ccr-19-3005.Peer-Reviewed Original ResearchConceptsMinimal residual diseaseMetastatic breast cancerDigital droplet PCRBreast cancerTumor mutationsResidual diseaseMRD detectionEarly-stage breast cancerCurative-intent treatmentCohort of patientsEarly-stage diseaseMedian lead timeClinical data collectionWhole-exome sequencingMRD testFirst positive sampleDistant recurrenceMost patientsMetastatic diagnosisStage 0PatientsPlasma samplingClinical sensitivityPatient-specific mutationsCfDNA samples