2023
Immunological and clinicopathological features predict HER2-positive breast cancer prognosis in the neoadjuvant NeoALTTO and CALGB 40601 randomized trials
Rediti M, Fernandez-Martinez A, Venet D, Rothé F, Hoadley K, Parker J, Singh B, Campbell J, Ballman K, Hillman D, Winer E, El-Abed S, Piccart M, Di Cosimo S, Symmans W, Krop I, Salgado R, Loi S, Pusztai L, Perou C, Carey L, Sotiriou C. Immunological and clinicopathological features predict HER2-positive breast cancer prognosis in the neoadjuvant NeoALTTO and CALGB 40601 randomized trials. Nature Communications 2023, 14: 7053. PMID: 37923752, PMCID: PMC10624889, DOI: 10.1038/s41467-023-42635-2.Peer-Reviewed Original ResearchConceptsEvent-free survivalHER2-positive breast cancerPathological complete responseCALGB 40601Breast cancerBreast pathological complete responseStromal tumor-infiltrating lymphocytesHormone receptor statusPhase III trialsClinical nodal statusIndependent prognostic factorTumor-infiltrating lymphocytesIdentification of patientsBreast cancer prognosisT cell receptorNeoadjuvant paclitaxelNeoadjuvant therapyIII trialsNodal statusComplete responsePrognostic factorsPrognostic scoreReceptor statusClinicopathological featuresResidual disease
2020
Survival, Pathologic Response, and Genomics in CALGB 40601 (Alliance), a Neoadjuvant Phase III Trial of Paclitaxel-Trastuzumab With or Without Lapatinib in HER2-Positive Breast Cancer.
Fernandez-Martinez A, Krop IE, Hillman DW, Polley MY, Parker JS, Huebner L, Hoadley KA, Shepherd J, Tolaney S, Henry NL, Dang C, Harris L, Berry D, Hahn O, Hudis C, Winer E, Partridge A, Perou CM, Carey LA. Survival, Pathologic Response, and Genomics in CALGB 40601 (Alliance), a Neoadjuvant Phase III Trial of Paclitaxel-Trastuzumab With or Without Lapatinib in HER2-Positive Breast Cancer. Journal Of Clinical Oncology 2020, 38: 4184-4193. PMID: 33095682, PMCID: PMC7723687, DOI: 10.1200/jco.20.01276.Peer-Reviewed Original ResearchConceptsPathologic complete responseRelapse-free survivalHuman epidermal growth factor receptor 2HER2-positive breast cancerBetter relapse-free survivalOverall survivalCALGB 40601Breast cancerImmune signaturesGene expression signaturesDe-escalation treatment strategiesPrediction of pCREnd pointEpidermal growth factor receptor 2Shorter relapse-free survivalPrimary end pointResidual disease groupSecondary end pointsUntreated stage IIGood prognostic factorGrowth factor receptor 2Phase III trialsExpression signaturesFactor receptor 2OS benefit
2018
Phase II Study of Taselisib (GDC-0032) in Combination with Fulvestrant in Patients with HER2-Negative, Hormone Receptor–Positive Advanced Breast Cancer
Dickler MN, Saura C, Richards DA, Krop IE, Cervantes A, Bedard PL, Patel MR, Pusztai L, Oliveira M, Cardenas AK, Cui N, Wilson TR, Stout TJ, Wei MC, Hsu JY, Baselga J. Phase II Study of Taselisib (GDC-0032) in Combination with Fulvestrant in Patients with HER2-Negative, Hormone Receptor–Positive Advanced Breast Cancer. Clinical Cancer Research 2018, 24: 4380-4387. PMID: 29793946, PMCID: PMC6139036, DOI: 10.1158/1078-0432.ccr-18-0613.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsClass I Phosphatidylinositol 3-KinasesDisease-Free SurvivalDrug-Related Side Effects and Adverse ReactionsFemaleFulvestrantHumansImidazolesMiddle AgedMutationOxazepinesReceptor, ErbB-2Receptors, EstrogenConceptsAdverse eventsClinical activityBreast cancerMutation statusOpen-label phase II studyHR-positive breast cancerHigher objective response rateConfirmatory phase III trialNCI CTCAE v4.0Median treatment durationObjective response ratePhase II studySerious adverse eventsNew safety signalsPhase III trialsPositive breast cancerClin Cancer ResIntramuscular fulvestrantMeasurable diseaseRECIST v1.1II studyIII trialsPostmenopausal womenUnacceptable toxicityTumor response
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 Research
2015
Molecular Heterogeneity and Response to Neoadjuvant Human Epidermal Growth Factor Receptor 2 Targeting in CALGB 40601, a Randomized Phase III Trial of Paclitaxel Plus Trastuzumab With or Without Lapatinib
Carey LA, Berry DA, Cirrincione CT, Barry WT, Pitcher BN, Harris LN, Ollila DW, Krop IE, Henry NL, Weckstein DJ, Anders CK, Singh B, Hoadley KA, Iglesia M, Cheang MC, Perou CM, Winer EP, Hudis CA. Molecular Heterogeneity and Response to Neoadjuvant Human Epidermal Growth Factor Receptor 2 Targeting in CALGB 40601, a Randomized Phase III Trial of Paclitaxel Plus Trastuzumab With or Without Lapatinib. Journal Of Clinical Oncology 2015, 34: 542-549. PMID: 26527775, PMCID: PMC4980567, DOI: 10.1200/jco.2015.62.1268.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCarcinomaEstrogen Receptor alphaFemaleGene ExpressionHumansImmunoglobulin GLapatinibMiddle AgedNeoadjuvant TherapyNeoplasm, ResidualPaclitaxelQuinazolinesReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneRNA, MessengerTrastuzumabTreatment OutcomeTumor MicroenvironmentTumor Suppressor Protein p53Young AdultConceptsPathologic complete response rateCALGB 40601Dual therapyIntrinsic subtypesHormone receptor-negative diseaseRandomized phase III trialHuman epidermal growth factor receptor 2End pointHER2-positive breast cancerEpidermal growth factor receptor 2Correlative end pointsDual HER2 blockadeHER2-positive diseaseComplete response ratePrimary end pointPhase III trialsProgression-free survivalReceptor-negative diseaseAddition of lapatinibGrowth factor receptor 2Immune cell signaturesFactor receptor 2Gene expression-based assaysMolecular featuresDual HER2Feasibility and Cardiac Safety of Trastuzumab Emtansine After Anthracycline-Based Chemotherapy As (neo)Adjuvant Therapy for Human Epidermal Growth Factor Receptor 2–Positive Early-Stage Breast Cancer
Krop IE, Suter TM, Dang CT, Dirix L, Romieu G, Zamagni C, Citron ML, Campone M, Xu N, Smitt M, Gianni L. Feasibility and Cardiac Safety of Trastuzumab Emtansine After Anthracycline-Based Chemotherapy As (neo)Adjuvant Therapy for Human Epidermal Growth Factor Receptor 2–Positive Early-Stage Breast Cancer. Journal Of Clinical Oncology 2015, 33: 1136-1142. PMID: 25713436, PMCID: PMC5657012, DOI: 10.1200/jco.2014.58.7782.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAnthracyclinesAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantCombined Modality TherapyCyclophosphamideDoxorubicinDrug Administration ScheduleEpirubicinFeasibility StudiesFluorouracilHeadacheHeart FailureHumansMaytansineMiddle AgedNauseaNeoplasm StagingReceptor, ErbB-2TrastuzumabTreatment OutcomeYoung AdultConceptsEarly-stage breast cancerHER2-positive early-stage breast cancerHuman epidermal growth factor receptorT-DM1Breast cancerEpidermal growth factor receptorGrowth factor receptorCardiac eventsCardiac safetyTrastuzumab emtansineSymptomatic congestive heart failureAsymptomatic LVEF declineCytotoxic agent DM1Planned radiation doseAnthracycline-based chemotherapyCoprimary end pointsPhase III trialsCongestive heart failureFactor receptorMetastatic breast cancerVentricular ejection fractionT-DM1 treatmentStage breast cancerLVEF declineAdverse events
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 ResearchTrastuzumab Emtansine: A Novel Antibody–Drug Conjugate for HER2-Positive Breast Cancer
Krop I, Winer EP. Trastuzumab Emtansine: A Novel Antibody–Drug Conjugate for HER2-Positive Breast Cancer. Clinical Cancer Research 2014, 20: 15-20. PMID: 24135146, DOI: 10.1158/1078-0432.ccr-13-0541.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerT-DM1Breast cancerAntibody-drug conjugatesAntibody-dependent cell-mediated cytotoxicityRecent phase III trialsHER2-positive breast cancerNovel antibody-drug conjugateCapecitabine/lapatinibFirst-line settingHepatic transaminase elevationsCombination of trastuzumabPhase II studyProgression-free survivalPhase III trialsInhibition of HER2Cell-mediated cytotoxicityFavorable toxicity profileHER2-positive tumor cellsMonoclonal antibody trastuzumabTransaminase elevationII studyIII trialsOverall survivalAdverse events
2013
Clinical and translational results of CALGB 40601: A neoadjuvant phase III trial of weekly paclitaxel and trastuzumab with or without lapatinib for HER2-positive breast cancer.
Carey L, Berry D, Ollila D, Harris L, Krop I, Weckstein D, Henry N, Anders C, Cirrincione C, Winer E, Perou C, Hudis C. Clinical and translational results of CALGB 40601: A neoadjuvant phase III trial of weekly paclitaxel and trastuzumab with or without lapatinib for HER2-positive breast cancer. Journal Of Clinical Oncology 2013, 31: 500-500. DOI: 10.1200/jco.2013.31.15_suppl.500.Peer-Reviewed Original ResearchHER2-positive breast cancerBreast pCR ratePathological complete responsePCR rateCALGB 40601Weekly paclitaxelResidual diseaseBreast cancerStage IIClinical stage IIDose-dense ACPhase III trialsProgression-free survivalHER2-targeted agentsBiomarkers of sensitivityGene copy number abnormalitiesTissue-based studiesEligible patientsNeoadjuvant settingNeoadjuvant studiesTH armPrimary endpointIII trialsMetastatic diseaseComplete response