2023
Standardized Definitions for Efficacy End Points in Neoadjuvant Breast Cancer Clinical Trials: NeoSTEEP
Litton J, Regan M, Pusztai L, Rugo H, Tolaney S, Garrett-Mayer E, Amiri-Kordestani L, Basho R, Best A, Boileau J, Denkert C, Foster J, Harbeck N, Jacene H, King T, Mason G, O'Sullivan C, Prowell T, Richardson A, Sepulveda K, Smith M, Tjoe J, Turashvili G, Woodward W, Butler L, Schwartz E, Korde L. Standardized Definitions for Efficacy End Points in Neoadjuvant Breast Cancer Clinical Trials: NeoSTEEP. Journal Of Clinical Oncology 2023, 41: 4433-4442. PMID: 37433103, PMCID: PMC10522109, DOI: 10.1200/jco.23.00435.Peer-Reviewed Original ResearchConceptsSecondary end pointsPathologic complete responseClinical trialsEnd pointStandardized definitionsHormone receptor-positive diseaseCurative-intent surgeryNeoadjuvant clinical trialsPathologic nodal evaluationResidual invasive cancerEfficacy end pointReceptor-positive diseaseBreast cancer clinical trialsResidual cancer burdenAlternative end pointsTrial end pointsRegional lymph nodesCancer end pointsCross-trial comparisonsSurvival end pointsEnd point definitionsCancer clinical trialsDrug Administration (FDA) regulatory considerationsEfficacy outcomesComplete responseEvaluation of the Sensitivity to Endocrine Therapy Index and 21-Gene Breast Recurrence Score in the SWOG S8814 Trial
Speers C, Symmans W, Barlow W, Trevarton A, The S, Du L, Rae J, Shak S, Baehner R, Sharma P, Pusztai L, Hortobagyi G, Hayes D, Albain K, Godwin A, Thompson A. Evaluation of the Sensitivity to Endocrine Therapy Index and 21-Gene Breast Recurrence Score in the SWOG S8814 Trial. Journal Of Clinical Oncology 2023, 41: 1841-1848. PMID: 36649570, PMCID: PMC10082279, DOI: 10.1200/jco.22.01499.Peer-Reviewed Original ResearchConceptsBreast Recurrence ScoreAnthracycline-based chemotherapyDisease-free survivalRecurrence scoreEndocrine therapyTherapy indexAdjuvant anthracycline-based chemotherapyNode-positive breast cancerAdjuvant endocrine therapyPrimary end pointSubset of patientsPostmenopausal patientsChemotherapy benefitTreatment armsPrognostic indexPrognostic informationBreast cancerPrognostic assessmentPrognostic performancePatientsEnd pointTumor samplesChemotherapyClinical validationProportional hazards assumption
2022
Impact of Circulating Tumor DNA–Based Detection of Molecular Residual Disease on the Conduct and Design of Clinical Trials for Solid Tumors
Kasi PM, Fehringer G, Taniguchi H, Starling N, Nakamura Y, Kotani D, Powles T, Li BT, Pusztai L, Aushev VN, Kalashnikova E, Sharma S, Malhotra M, Demko ZP, Aleshin A, Rodriguez A, Billings PR, Grothey A, Taieb J, Cunningham D, Yoshino T, Kopetz S. Impact of Circulating Tumor DNA–Based Detection of Molecular Residual Disease on the Conduct and Design of Clinical Trials for Solid Tumors. JCO Precision Oncology 2022, 6: e2100181. PMID: 35263168, PMCID: PMC8926064, DOI: 10.1200/po.21.00181.Peer-Reviewed Original ResearchConceptsMolecular residual diseaseSurrogate end pointsCtDNA testingMRD detectionResidual diseaseClinical trialsCancer recurrenceTumor DNAEnd pointMRD-positive patientsUse of ctDNAHigh-risk categoryCtDNA dynamicsTrial enrichmentAccelerated approvalDifferent cancer typesCancer managementClinical utilityHigh riskClinical practiceSmall cohortSolid tumorsRecurrenceTrial durationTreatment assignment
2020
Effect of Pembrolizumab Plus Neoadjuvant Chemotherapy on Pathologic Complete Response in Women With Early-Stage Breast Cancer
Nanda R, Liu MC, Yau C, Shatsky R, Pusztai L, Wallace A, Chien AJ, Forero-Torres A, Ellis E, Han H, Clark A, Albain K, Boughey JC, Jaskowiak NT, Elias A, Isaacs C, Kemmer K, Helsten T, Majure M, Stringer-Reasor E, Parker C, Lee MC, Haddad T, Cohen RN, Asare S, Wilson A, Hirst GL, Singhrao R, Steeg K, Asare A, Matthews JB, Berry S, Sanil A, Schwab R, Symmans WF, van ‘t Veer L, Yee D, DeMichele A, Hylton NM, Melisko M, Perlmutter J, Rugo HS, Berry DA, Esserman LJ. Effect of Pembrolizumab Plus Neoadjuvant Chemotherapy on Pathologic Complete Response in Women With Early-Stage Breast Cancer. JAMA Oncology 2020, 6: 676-684. PMID: 32053137, PMCID: PMC7058271, DOI: 10.1001/jamaoncol.2019.6650.Peer-Reviewed Original ResearchConceptsEarly-stage breast cancerPathologic complete responseNeoadjuvant chemotherapyPhase 3 trialResidual cancer burdenStandard neoadjuvant chemotherapyBreast cancerComplete responseInvestigational armStage II/III breast cancerHigher event-free survival rateERBB2-negative breast cancerEvent-free survival rateAnthracycline-based neoadjuvant chemotherapyDistant recurrence-free survivalEnd pointTriple-negative breast cancerCycles of pembrolizumabEffect of pembrolizumabImmune-related endocrinopathiesNeoadjuvant clinical trialsTriple-negative cohortPrimary end pointSecondary end pointsRecurrence-free survival
2011
Recommendations from an International Consensus Conference on the Current Status and Future of Neoadjuvant Systemic Therapy in Primary Breast Cancer
Kaufmann M, von Minckwitz G, Mamounas EP, Cameron D, Carey LA, Cristofanilli M, Denkert C, Eiermann W, Gnant M, Harris JR, Karn T, Liedtke C, Mauri D, Rouzier R, Ruckhaeberle E, Semiglazov V, Symmans WF, Tutt A, Pusztai L. Recommendations from an International Consensus Conference on the Current Status and Future of Neoadjuvant Systemic Therapy in Primary Breast Cancer. Annals Of Surgical Oncology 2011, 19: 1508-1516. PMID: 22193884, DOI: 10.1245/s10434-011-2108-2.Peer-Reviewed Original ResearchConceptsNeoadjuvant systemic therapyPrimary breast cancerBreast cancerSystemic therapyBreast-conserving surgery rateLarge adjuvant trialsPathologic complete responseInflammatory breast cancerNew therapeutic regimensIntermediate end pointsInternational Consensus ConferenceClinical research groupAdjuvant trialsNew regimensPathologic responseComplete responseSurgery ratesTherapeutic regimensConsensus conferenceEnd pointTherapyCancerTrialsRegimensPanel of representatives
2008
Research Issues Affecting Preoperative Systemic Therapy for Operable Breast Cancer
Wolff AC, Berry D, Carey LA, Colleoni M, Dowsett M, Ellis M, Garber JE, Mankoff D, Paik S, Pusztai L, Smith ML, Zujewski J. Research Issues Affecting Preoperative Systemic Therapy for Operable Breast Cancer. Journal Of Clinical Oncology 2008, 26: 806-813. PMID: 18258990, DOI: 10.1200/jco.2007.15.2983.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAntineoplastic AgentsApoptosisBiomarkersBiomedical ResearchBreast NeoplasmsCell ProliferationEpidemiologic Research DesignErbB ReceptorsEthics, ClinicalFemaleGene Expression ProfilingHumansMastectomy, SegmentalNeoadjuvant TherapyPatient AdvocacyPreoperative CarePrognosisReceptors, SteroidTreatment OutcomeConceptsPreoperative systemic therapyOperable breast cancerSystemic therapyBreast cancerTrial designEnd pointCohesive multidisciplinary teamBreast conservation ratesEffective alternative therapyTrial end pointsLong-term outcomesSpecific breast cancer subtypesPredictors of responseNovel trial designsIntermediate end pointsBreast cancer subtypesIndividual patient subgroupsAdjuvant trialsPatient subgroupsSmall trialsAlternative therapiesMAIN OUTCOMEClinical careCancer subtypesMultidisciplinary team