2024
Phase Ib dose-escalation trial of taselisib (GDC-0032) in combination with HER2-directed therapies in patients with advanced HER2+ breast cancer
Grinshpun A, Ren S, Graham N, DeMeo M, Wrabel E, Carter J, Tayob N, Pereslete A, Hamilton E, Juric D, Mayer E, Tolaney S, Krop I, Metzger O. Phase Ib dose-escalation trial of taselisib (GDC-0032) in combination with HER2-directed therapies in patients with advanced HER2+ breast cancer. ESMO Open 2024, 9: 103465. PMID: 38833970, PMCID: PMC11179085, DOI: 10.1016/j.esmoop.2024.103465.Peer-Reviewed Original ResearchProgression-free survivalMaximal tolerated doseHER2+ breast cancerAdverse eventsBreast cancerT-DM1Cohort AHuman epidermal growth factor receptor 2-positiveEpidermal growth factor receptor 2-positiveHER2+) breast cancerMedian progression-free survivalAll-grade adverse eventsAssociated with significant toxicityCirculating tumor DNA analysisDevelopment of acquired resistanceHER2-directed regimensHER2-directed therapyAnti-HER2 therapyHER2-targeted therapyPhase Ib studyTumor DNA analysisPI3KDose escalationImprove disease controlOral inhibitorPrediction of Benefit From Adjuvant Pertuzumab by 80-Gene Signature in the APHINITY (BIG 4-11) Trial
Krop I, Mittempergher L, Paulson J, Andre F, Bonnefoi H, Loi S, Loibl S, Gelber R, Caballero C, Bhaskaran R, Dreezen C, Menicucci A, Bernards R, van ’t Veer L, Piccart M. Prediction of Benefit From Adjuvant Pertuzumab by 80-Gene Signature in the APHINITY (BIG 4-11) Trial. JCO Precision Oncology 2024, 8: e2200667. PMID: 38237097, DOI: 10.1200/po.22.00667.Peer-Reviewed Original ResearchConceptsInvasive disease-free survivalHER2 typeLuminal typeInvasive disease-free survival eventsHazard ratioEarly-stage breast cancerLuminal-type tumorsMolecular subtype signaturesAnti-HER2 therapyHER2-positive tumorsDisease-free survivalStandard adjuvant chemotherapyBasal-type tumorsBasal typePredictive of benefitAdjuvant pertuzumabAPHINITY trialHER2-typeHER2-positiveInferior prognosisAdjuvant chemotherapyTumor subtypesNo significant differenceAnti-HER2Breast tumors
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
2022
Phase Ib study of pembrolizumab in combination with trastuzumab emtansine for metastatic HER2-positive breast cancer
Waks AG, Keenan TE, Li T, Tayob N, Wulf GM, Richardson ET, Attaya V, Anderson L, Mittendorf EA, Overmoyer B, Winer EP, Krop IE, Agudo J, Van Allen EM, Tolaney SM. Phase Ib study of pembrolizumab in combination with trastuzumab emtansine for metastatic HER2-positive breast cancer. Journal For ImmunoTherapy Of Cancer 2022, 10: e005119. PMID: 36252998, PMCID: PMC9577940, DOI: 10.1136/jitc-2022-005119.Peer-Reviewed Original ResearchConceptsObjective response rateProgression-free survivalMetastatic breast cancerAdverse eventsBreast cancerT-DM1Immune biomarkersTrastuzumab emtansineHER2-positive metastatic breast cancerMetastatic HER2-positive breast cancerGrade 3 adverse eventsMedian progression-free survivalTreatment-related adverse eventsHuman epidermal growth factor receptor 2Cell death ligand 1HER2-positive breast cancerEpidermal growth factor receptor 2Dose-finding cohortPhase 2 dosePhase Ib studyPhase Ib trialAnti-HER2 therapyDose-limiting toxicityGrowth factor receptor 2Immune checkpoint blockadeLocal Therapy Outcomes and Toxicity From the ATEMPT Trial (TBCRC 033): A Phase II Randomized Trial of Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab in Women With Stage I HER2-Positive Breast Cancer
Bellon JR, Tayob N, Yang DD, Tralins J, Dang CT, Isakoff SJ, DeMeo M, Burstein HJ, Partridge AH, Winer EP, Krop IE, Tolaney SM. Local Therapy Outcomes and Toxicity From the ATEMPT Trial (TBCRC 033): A Phase II Randomized Trial of Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab in Women With Stage I HER2-Positive Breast Cancer. International Journal Of Radiation Oncology • Biology • Physics 2022, 113: 117-124. PMID: 34990776, DOI: 10.1016/j.ijrobp.2021.12.173.Peer-Reviewed Original ResearchConceptsHER2-positive breast cancerBreast-conserving surgeryStage I HER2-positive breast cancerT-DM1 armBreast radiation therapyT-DM1Radiation therapySkin toxicityBreast cancerBCS patientsWBRT patientsInvasive disease-free survival eventsDisease-free survival eventsInvasive disease-free survivalHuman epidermal growth factor receptor 2Phase II Randomized TrialWhole breast radiation therapyEpidermal growth factor receptor 2Adjuvant T-DM1Adjuvant trastuzumab emtansineEfficacy of HER2RT-related toxicityWeeks of therapyAcute skin toxicityAnti-HER2 therapy
2021
Local Therapy Outcomes and Toxicity From the ATEMPT Trial (TBCRC 033), a Phase II Randomized Trial of Adjuvant T-DM1 vs. TH in Women With Stage I HER2 Positive Breast Cancer
Bellon J, Tayob N, Burstein H, Partridge A, Demeo M, Tralins J, Yang D, Dang C, Isakoff S, Yardley D, Valero V, Winer E, Krop I, Tolaney S. Local Therapy Outcomes and Toxicity From the ATEMPT Trial (TBCRC 033), a Phase II Randomized Trial of Adjuvant T-DM1 vs. TH in Women With Stage I HER2 Positive Breast Cancer. International Journal Of Radiation Oncology • Biology • Physics 2021, 111: s34. DOI: 10.1016/j.ijrobp.2021.07.103.Peer-Reviewed Original ResearchT-DM1 armBreast conserving surgeryPartial breast irradiationT-DM1Radiation therapyBreast cancerLocal recurrenceSkin toxicityGrade 2 acute skin toxicityProspective randomized phase II studyGrade 3 skin toxicityHormone receptor-positive diseaseRandomized phase II studyPhase II Randomized TrialAdjuvant T-DM1Conclusions Radiation therapyGrade 2 pneumonitisGrade 3 pneumonitisIpsilateral rib fracturesPhase II studyReceptor-positive diseaseWeeks of therapyAcute skin toxicityAnti-HER2 therapyNodal radiation therapyFOXA1 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 upregulationLapatinibThe efficacy and safety of enzalutamide with trastuzumab in patients with HER2+ and androgen receptor-positive metastatic or locally advanced breast cancer
Wardley A, Cortes J, Provencher L, Miller K, Chien AJ, Rugo HS, Steinberg J, Sugg J, Tudor IC, Huizing M, Young R, Abramson V, Bose R, Hart L, Chan S, Cameron D, Wright GS, Graas MP, Neven P, Rocca A, Russo S, Krop IE. The efficacy and safety of enzalutamide with trastuzumab in patients with HER2+ and androgen receptor-positive metastatic or locally advanced breast cancer. Breast Cancer Research And Treatment 2021, 187: 155-165. PMID: 33591468, PMCID: PMC8062601, DOI: 10.1007/s10549-021-06109-7.Peer-Reviewed Original ResearchConceptsTreatment-emergent adverse eventsProgression-free survivalSafety of enzalutamideBreast cancerSerious treatment-emergent adverse eventsEastern Cooperative Oncology Group statusMedian progression-free survivalPrior anti-HER2 therapyEnd pointHuman epidermal growth factor receptorClinical benefit rateDurable stable diseaseSolid Tumors v1.1Primary end pointSecondary end pointsAdvanced breast cancerAnti-HER2 therapyHormone receptor statusResponse Evaluation CriteriaSubset of patientsAR expression levelsTrastuzumab-resistant HER2Durable disease controlMalignant neoplasm progressionAnti-HER2 antibody
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
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 PTENGenomic-based predictive biomarkers to anti-HER2 therapies: A combined analysis of CALGB 40601 (Alliance) and PAMELA clinical trials.
Fernandez-Martinez A, Tanioka M, Fan C, Parker J, Hoadley K, Krop I, Cortes J, Llombart Cussac A, Nuciforo P, Galván P, Pascual T, Partridge A, Prat A, Carey L, Perou C. Genomic-based predictive biomarkers to anti-HER2 therapies: A combined analysis of CALGB 40601 (Alliance) and PAMELA clinical trials. Journal Of Clinical Oncology 2019, 37: 571-571. DOI: 10.1200/jco.2019.37.15_suppl.571.Peer-Reviewed Original ResearchHER2-E subtypeCALGB 40601Clinical trialsPredictive biomarkersIntrinsic subtypesEvent-free survival analysisHER2-positive breast cancerAnti-HER2 combinationDual HER2 blockadeAnti-HER2 therapyAnti-HER2 treatmentIndependent predictive biomarkerFree survival analysisPre-treatment tumorsERBB2 mRNA levelsHER2 blockadeLuminal signatureNeoadjuvant settingPCR rateIndependent predictorsLuminal ALuminal BSubtype distributionBreast cancerERBB2 mRNALocal–regional recurrence in women with small node-negative, HER2-positive breast cancer: results from a prospective multi-institutional study (the APT trial)
Bellon JR, Guo H, Barry WT, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis M, Wolff AC, Carey LA, Overmoyer BA, Partridge AH, Hudis CA, Krop I, Burstein HJ, Winer EP, Tolaney SM. Local–regional recurrence in women with small node-negative, HER2-positive breast cancer: results from a prospective multi-institutional study (the APT trial). Breast Cancer Research And Treatment 2019, 176: 303-310. PMID: 31004299, DOI: 10.1007/s10549-019-05238-4.Peer-Reviewed Original ResearchConceptsHER2-positive breast cancerLocal-regional recurrenceDisease-free survivalEffective anti-HER2 therapyLRR-free survivalAnti-HER2 therapyBreast-conserving surgeryBreast cancerRadiation therapySystemic therapyHormone receptor-positive tumorsProspective multi-institutional studyHER2-negative diseaseHER2-positive diseaseNegative axillary nodesEffective systemic therapyProspective multicenter trialEarly-stage patientsKaplan-Meier methodReceptor-positive tumorsHER2-positive tumorsMulti-institutional studyFuture investigational effortsAdjuvant trastuzumabProtocol therapy
2018
369TiP PATINA: A randomized, open label, phase III trial to evaluate the efficacy and safety of palbociclib + Anti-HER2 therapy + endocrine therapy (ET) vs. anti-HER2 therapy + ET after induction treatment for hormone receptor positive (HR+)/HER2-positive metastatic breast cancer (MBC)
Loibl S, Metzger O, Mandrekar S, Mundhenke C, Seiler S, Valagussa P, DeMichele A, Lim E, Tripathy D, Winer E, Huang C, Carey L, Francis P, Miller K, Goetz M, Prat A, Loi S, Krop I, Gianni L, Ciruelos E. 369TiP PATINA: A randomized, open label, phase III trial to evaluate the efficacy and safety of palbociclib + Anti-HER2 therapy + endocrine therapy (ET) vs. anti-HER2 therapy + ET after induction treatment for hormone receptor positive (HR+)/HER2-positive metastatic breast cancer (MBC). Annals Of Oncology 2018, 29: viii121. DOI: 10.1093/annonc/mdy272.357.Peer-Reviewed Original Research
2017
324TiP PATINA: A randomized open label phase III trial to evaluate the efficacy and safety of palbociclib + anti HER2 therapy + endocrine therapy vs anti HER2 therapy + endocrine therapy after induction treatment for hormone receptor positive, HER2-positive metastatic breast cancer
Metzger O, Mandrekar S, Ciruelos E, Loibl S, Valagussa P, Demichele A, Lim E, Tripathy D, Winer E, Huang C, Khoeler M, Carey L, Francis P, Miller K, Goel S, Goetz M, Prat A, Loi S, Krop I, Gianni L. 324TiP PATINA: A randomized open label phase III trial to evaluate the efficacy and safety of palbociclib + anti HER2 therapy + endocrine therapy vs anti HER2 therapy + endocrine therapy after induction treatment for hormone receptor positive, HER2-positive metastatic breast cancer. Annals Of Oncology 2017, 28: v107-v108. DOI: 10.1093/annonc/mdx365.087.Peer-Reviewed Original ResearchA phase II study of eribulin mesylate in combination with trastuzumab and pertuzumab in patients (pts) with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC).
Luis I, Guo H, Barry W, Krop I, Wagle N, Lowe A, Gore D, Andrews C, Osmani W, Isakoff S, Tung N, Winer E, Lin N, Freedman R. A phase II study of eribulin mesylate in combination with trastuzumab and pertuzumab in patients (pts) with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC). Journal Of Clinical Oncology 2017, 35: 1034-1034. DOI: 10.1200/jco.2017.35.15_suppl.1034.Peer-Reviewed Original ResearchMetastatic breast cancerOverall response ratePhase II studyStable diseasePertuzumab exposureAdverse eventsII studyCohort AHuman epidermal growth factor receptorActivity of eribulinDose of eribulinFrequent grade 3First-line settingMost adverse eventsAnti-HER2 therapyCorrelative studiesEpidermal growth factor receptorCell-free DNAGrowth factor receptorHematologic toxicityCohort studyOverall survivalPartial responseCohort BSingle centerA 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
2011
Responses to subsequent anti-HER2 therapy after treatment with trastuzumab-DM1 in women with HER2-positive metastatic breast cancer
Olson EM, Lin NU, DiPiro PJ, Najita JS, Krop IE, Winer EP, Burstein HJ. Responses to subsequent anti-HER2 therapy after treatment with trastuzumab-DM1 in women with HER2-positive metastatic breast cancer. Annals Of Oncology 2011, 23: 93-97. PMID: 21531783, PMCID: PMC3276325, DOI: 10.1093/annonc/mdr061.Peer-Reviewed Original ResearchConceptsAnti-HER2 therapyMetastatic breast cancerHER2-positive MBC patientsT-DM1MBC patientsBreast cancerHER2-positive metastatic breast cancerSingle-agent T-DM1Positive metastatic breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Blinded radiology reviewAnti-HER2 agentsGrowth factor receptor 2Kaplan-Meier estimatesFurther clinical benefitFactor receptor 2Protocol therapyMedian durationFurther therapyPartial responseRadiology reviewClinical benefitSubsequent linesMetastatic therapy