2022
The oral selective estrogen receptor degrader GDC-0810 (ARN-810) in postmenopausal women with hormone receptor-positive HER2-negative (HR + /HER2 −) advanced/metastatic breast cancer
Bardia A, Mayer I, Winer E, Linden H, Ma C, Parker B, Bellet M, Arteaga C, Cheeti S, Gates M, Chang C, Fredrickson J, Spoerke J, Moore H, Giltnane J, Friedman L, Chow Maneval E, Chan I, Jhaveri K. The oral selective estrogen receptor degrader GDC-0810 (ARN-810) in postmenopausal women with hormone receptor-positive HER2-negative (HR + /HER2 −) advanced/metastatic breast cancer. Breast Cancer Research And Treatment 2022, 197: 319-331. PMID: 36401732, PMCID: PMC9823088, DOI: 10.1007/s10549-022-06797-9.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerSelective estrogen receptor degraderDose escalationESR1 mutationsPostmenopausal womenBreast cancerEstrogen receptorCombination treatmentNon-complete response/non-progressive diseaseAdvanced/Metastatic Breast CancerOral selective estrogen receptor degraderPreliminary anti-tumor activityESR1 mutation statusPhase 2 dosePlasma ctDNA samplesCommon adverse eventsNon-progressive diseaseDose-limiting toxicityHormone-releasing hormoneSelective estrogen receptorAnti-tumor activityStable diseaseAdverse eventsPartial responseProgressive diseaseThe feasibility of using an autologous GM-CSF-secreting breast cancer vaccine to induce immunity in patients with stage II–III and metastatic breast cancers
Anderson KS, Erick TK, Chen M, Daley H, Campbell M, Colson Y, Mihm M, Zakka LR, Hopper M, Barry W, Winer EP, Dranoff G, Overmoyer B. The feasibility of using an autologous GM-CSF-secreting breast cancer vaccine to induce immunity in patients with stage II–III and metastatic breast cancers. Breast Cancer Research And Treatment 2022, 194: 65-78. PMID: 35482127, PMCID: PMC9046531, DOI: 10.1007/s10549-022-06562-y.Peer-Reviewed Original ResearchConceptsBreast cancer vaccinesAutologous GM-CSFBreast cancerMetastatic diseaseGM-CSFStage IICancer vaccinesTumor cellsEvidence of diseaseStart of vaccinationInjection site reactionsMetastatic breast cancerUpper respiratory symptomsImmune cell infiltrationRole of vaccinationReplication-defective adenoviral vectorEvaluable patientsMethodsTumor cellsStable diseaseWeekly vaccinationsJoint painProgressive diseaseRespiratory symptomsFifth injectionTRIAL REGISTRATIONThe Phase II MutHER Study of Neratinib Alone and in Combination with Fulvestrant in HER2-Mutated, Non-amplified Metastatic Breast CancerNeratinib and Fulvestrant in HER2-Mutated Breast Cancer
X. C, Luo J, Freedman RA, Pluard TJ, Nangia JR, Lu J, Valdez-Albini F, Cobleigh M, Jones JM, Lin NU, Winer EP, Marcom PK, Thomas S, Anderson J, Haas B, Bucheit L, Bryce R, Lalani AS, Carey LA, Goetz MP, Gao F, Kimmick G, Pegram MD, Ellis MJ, Bose R. The Phase II MutHER Study of Neratinib Alone and in Combination with Fulvestrant in HER2-Mutated, Non-amplified Metastatic Breast CancerNeratinib and Fulvestrant in HER2-Mutated Breast Cancer. Clinical Cancer Research 2022, 28: 1258-1267. PMID: 35046057, DOI: 10.1158/1078-0432.ccr-21-3418.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerBreast cancerER cohortEstrogen receptor-positive breast cancerReceptor-positive breast cancerClinical benefit rateDual HER2 blockadePhase II trialEfficacy of neratinibHER2 blockadeNeratinib monotherapyStable diseaseII trialHER2 mutationsLobular histologyPartial responseEndocrine resistanceBenefit ratePatientsFurther evaluationCancerFulvestrantHER2NeratinibProgression
2021
Clinical Efficacy and Molecular Response Correlates of the WEE1 Inhibitor Adavosertib Combined with Cisplatin in Patients with Metastatic Triple-Negative Breast Cancer
Keenan TE, Li T, Vallius T, Guerriero JL, Tayob N, Kochupurakkal B, Davis J, Pastorello R, Tahara RK, Anderson L, Conway J, He MX, Shannon E, Godin RE, Sorger PK, D'Andrea A, Overmoyer B, Winer EP, Mittendorf EA, Van Allen EM, Shapiro GI, Tolaney SM. Clinical Efficacy and Molecular Response Correlates of the WEE1 Inhibitor Adavosertib Combined with Cisplatin in Patients with Metastatic Triple-Negative Breast Cancer. Clinical Cancer Research 2021, 27: 983-991. PMID: 33257427, PMCID: PMC7887044, DOI: 10.1158/1078-0432.ccr-20-3089.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerObjective response rateTriple-negative breast cancerWEE1 inhibitor adavosertibPrior linesClinical benefitBreast cancerMedian progression-free survivalTreatment-related grade 3One-sided type I errorImmune-infiltrated tumorsPhase II studyProgression-free survivalT cell infiltrationImmune gene expressionPrior chemotherapyStable diseaseProtocol therapyII studyPartial responseAdverse eventsMedian ageClinical efficacyGrade 3Tumor biopsies
2020
Phase 2 study of buparlisib (BKM120), a pan-class I PI3K inhibitor, in patients with metastatic triple-negative breast cancer
Garrido-Castro AC, Saura C, Barroso-Sousa R, Guo H, Ciruelos E, Bermejo B, Gavilá J, Serra V, Prat A, Paré L, Céliz P, Villagrasa P, Li Y, Savoie J, Xu Z, Arteaga CL, Krop IE, Solit DB, Mills GB, Cantley LC, Winer EP, Lin NU, Rodon J. Phase 2 study of buparlisib (BKM120), a pan-class I PI3K inhibitor, in patients with metastatic triple-negative breast cancer. Breast Cancer Research 2020, 22: 120. PMID: 33138866, PMCID: PMC7607628, DOI: 10.1186/s13058-020-01354-y.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAminopyridinesAntineoplastic Combined Chemotherapy ProtocolsClass I Phosphatidylinositol 3-KinasesDisease ProgressionFemaleHigh-Throughput Nucleotide SequencingHumansMiddle AgedMorpholinesNeoplasm MetastasisPatient SafetyProtein Kinase InhibitorsProteomicsResponse Evaluation Criteria in Solid TumorsSurvival RateTreatment OutcomeTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerProgression-free survivalPan-class I PI3K inhibitorMetastatic triple-negative breast cancerStable diseasePhase 2 studyBreast cancerOverall survivalPI3K inhibitorsPI3K pathwayPartial responseComplete responseClinical benefitSingle-arm phase 2 studyTriple-negative metastatic breast cancerMedian progression-free survivalK inhibitorsClinical benefit rateEfficacy of buparlisibK pathwayFrequent adverse eventsMedian overall survivalPercent of patientsMetastatic breast cancerSubset of patients
2019
Ribociclib Plus Trastuzumab in Advanced HER2-Positive Breast Cancer: Results of a Phase 1b/2 Trial
Goel S, Pernas S, Tan-Wasielewski Z, Barry WT, Bardia A, Rees R, Andrews C, Tahara RK, Trippa L, Mayer EL, Winer EP, Spring LM, Tolaney SM. Ribociclib Plus Trastuzumab in Advanced HER2-Positive Breast Cancer: Results of a Phase 1b/2 Trial. Clinical Breast Cancer 2019, 19: 399-404. PMID: 31235441, DOI: 10.1016/j.clbc.2019.05.010.Peer-Reviewed Original ResearchConceptsHER2-positive breast cancerAdvanced HER2-positive breast cancerProgression-free survivalBreast cancerAdverse eventsObjective responseGrade 3 adverse eventsGrade 4/5 adverse eventsHormone receptor-positive diseaseMedian progression-free survivalAnti-HER2 combinationClinical benefit rateHER2-negative diseasePhase 1b/2 studyPhase 1b/2 trialPrior therapy linesReceptor-positive diseaseAnti-HER2 therapyNew safety concernsCyclin-dependent kinase 4Stable diseaseExpansion cohortMetastatic settingPrior linesQTc prolongationPembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 study
Adams S, Loi S, Toppmeyer D, Cescon DW, De Laurentiis M, Nanda R, Winer EP, Mukai H, Tamura K, Armstrong A, Liu MC, Iwata H, Ryvo L, Wimberger P, Rugo HS, Tan AR, Jia L, Ding Y, Karantza V, Schmid P. Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 study. Annals Of Oncology 2019, 30: 405-411. PMID: 30475947, DOI: 10.1093/annonc/mdy518.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerPositive metastatic triple-negative breast cancerTreatment-related adverse eventsTriple-negative breast cancerDisease control rateObjective response rateFirst-line therapyProgression-free survivalAdverse eventsPD-L1Stable diseasePembrolizumab monotherapyOverall survivalCohort BControl rateBreast cancerResponse ratePD-L1 combined positive scoreCentral nervous system metastasesGrade 4 adverse eventsMedian progression-free survivalStandard first-line treatmentEnd pointGrade 3 severityManageable safety profile
2017
Neratinib Efficacy and Circulating Tumor DNA Detection of HER2 Mutations in HER2 Nonamplified Metastatic Breast Cancer
X. C, Bose R, Gao F, Freedman RA, Telli ML, Kimmick G, Winer E, Naughton M, Goetz MP, Russell C, Tripathy D, Cobleigh M, Forero A, Pluard TJ, Anders C, Niravath PA, Thomas S, Anderson J, Bumb C, Banks KC, Lanman RB, Bryce R, Lalani AS, Pfeifer J, Hayes DF, Pegram M, Blackwell K, Bedard PL, Al-Kateb H, Ellis MJC. Neratinib Efficacy and Circulating Tumor DNA Detection of HER2 Mutations in HER2 Nonamplified Metastatic Breast Cancer. Clinical Cancer Research 2017, 23: 5687-5695. PMID: 28679771, PMCID: PMC6746403, DOI: 10.1158/1078-0432.ccr-17-0900.Peer-Reviewed Original ResearchConceptsClinical benefit rateProgression-free survivalMetastatic breast cancerStable diseaseCtDNA sequencingMedian progression-free survivalSingle-arm phase II trialCommon adverse eventsPhase II trialClinical trial participationPromising preclinical dataClin Cancer ResTumor-positive casesVariant allele frequencyProphylactic loperamideSecondary endpointsII trialPartial responseAdverse eventsTrial participationPreclinical dataBenefit rateBreast cancerWeek 4Estrogen receptorA 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 centerPhase II and Biomarker Study of Cabozantinib in Metastatic Triple‐Negative Breast Cancer Patients
Tolaney SM, Ziehr DR, Guo H, Ng MR, Barry WT, Higgins MJ, Isakoff SJ, Brock JE, Ivanova EV, Paweletz CP, Demeo MK, Ramaiya NH, Overmoyer BA, Jain RK, Winer EP, Duda DG. Phase II and Biomarker Study of Cabozantinib in Metastatic Triple‐Negative Breast Cancer Patients. The Oncologist 2017, 22: 25-32. PMID: 27789775, PMCID: PMC5313267, DOI: 10.1634/theoncologist.2016-0229.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnilidesBiomarkers, TumorDisease-Free SurvivalFemaleHumansKaplan-Meier EstimateMiddle AgedMolecular Targeted TherapyNeoplasm MetastasisPlacenta Growth FactorProtein Kinase InhibitorsProto-Oncogene Proteins c-metPyridinesTriple Negative Breast NeoplasmsVascular Endothelial Growth Factor DVascular Endothelial Growth Factor Receptor-2ConceptsProgression-free survivalVascular endothelial growth factorBreast cancer patientsStable diseasePrimary endpointPartial responseCancer patientsBreast cancerMetastatic triple-negative breast cancer patientsMedian progression-free survivalSingle-arm phase IILonger progression-free survivalTriple-negative breast cancer patientsSoluble VEGF receptor 2Plasma placental growth factorTriple-negative breast cancerBiomarker studiesGrowth factorClinical benefit rateCytotoxic lymphocyte populationsGrade 4 toxicityObjective response ratePalmar-plantar erythrodysesthesiaSubset of patientsStromal cell-derived factor 1a
2016
Cabozantinib for metastatic breast carcinoma: results of a phase II placebo-controlled randomized discontinuation study
Tolaney SM, Nechushtan H, Ron IG, Schöffski P, Awada A, Yasenchak CA, Laird AD, O’Keeffe B, Shapiro GI, Winer EP. Cabozantinib for metastatic breast carcinoma: results of a phase II placebo-controlled randomized discontinuation study. Breast Cancer Research And Treatment 2016, 160: 305-312. PMID: 27714541, PMCID: PMC5065609, DOI: 10.1007/s10549-016-4001-y.Peer-Reviewed Original ResearchConceptsObjective response rateProgression-free survivalOverall survivalStable diseaseMBC patientsWeek 12Common grade 3/4 adverse eventsOverall median progression-free survivalGrade 3/4 adverse eventsMedian progression-free survivalSolid Tumors version 1.0Metastatic breast cancer patientsOral tyrosine kinase inhibitorResultsForty-five patientsDisease control rateMedian overall survivalPalmar-plantar erythrodysesthesiaResponse Evaluation CriteriaMetastatic breast carcinomaBreast cancer patientsTyrosine kinase inhibitorsCabozantinib monotherapyDiscontinuation studyPrimary endpointRespiratory failure
2015
SU2C Phase Ib Study of Paclitaxel and MK-2206 in Advanced Solid Tumors and Metastatic Breast Cancer
Gonzalez-Angulo AM, Krop I, Akcakanat A, Chen H, Liu S, Li Y, Culotta KS, Tarco E, Piha-Paul S, Moulder-Thompson S, Velez-Bravo V, Sahin AA, Doyle LA, Do KA, Winer EP, Mills GB, Kurzrock R, Meric-Bernstam F. SU2C Phase Ib Study of Paclitaxel and MK-2206 in Advanced Solid Tumors and Metastatic Breast Cancer. Journal Of The National Cancer Institute 2015, 107: dju493. PMID: 25688104, PMCID: PMC4342675, DOI: 10.1093/jnci/dju493.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsDrug Administration ScheduleDrug EruptionsFatigueFemaleHeterocyclic Compounds, 3-RingHumansHyperglycemiaMaleMaximum Tolerated DoseMiddle AgedNeoplasmsNeutropeniaPaclitaxelSeverity of Illness IndexTreatment OutcomeConceptsDose escalationDay 1Day 2Higher adverse eventsPhase Ib studyWeeks of therapyAdvanced solid tumorsCTCAE grade 3Metastatic breast cancerPrevious phase IPreliminary antitumor activityDose expansionStable diseaseObjective responseUnacceptable toxicityAdverse eventsMedian ageWeekly dosesClinical benefitPharmacodynamic markersSystemic exposureExcessive toxicityTumor responseGrade 3Median number
2013
A Phase I dose-escalation study of the VEGFR inhibitor tivozanib hydrochloride with weekly paclitaxel in metastatic breast cancer
Mayer EL, Scheulen ME, Beckman J, Richly H, Duarte A, Cotreau MM, Strahs AL, Agarwal S, Steelman L, Winer EP, Dickler MN. A Phase I dose-escalation study of the VEGFR inhibitor tivozanib hydrochloride with weekly paclitaxel in metastatic breast cancer. Breast Cancer Research And Treatment 2013, 140: 331-339. PMID: 23868188, DOI: 10.1007/s10549-013-2632-9.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsDose-Response Relationship, DrugDrug-Related Side Effects and Adverse ReactionsFemaleHumansMiddle AgedNeoplasm MetastasisPaclitaxelPhenylurea CompoundsProtein Kinase InhibitorsQuinolinesVascular Endothelial Growth Factor Receptor-1ConceptsMetastatic breast cancerTyrosine kinase inhibitorsWeekly paclitaxelPaclitaxel 90Breast cancerPhase I dose-escalation studyI dose-escalation studyVascular endothelial growth factor receptor 1Activity of tivozanibSafety/tolerabilityGrade 3/4 toxicitiesPeripheral sensory neuropathyPhase Ib studyDose-escalation studyResponse Evaluation CriteriaSelective tyrosine kinase inhibitorVEGFR-TKI treatmentSolid Tumors responseGrowth factor receptor 1Influence of paclitaxelFactor receptor 1Stable diseaseMBC patientsPartial responseProgressive disease
2012
Combination antiangiogenic therapy in advanced breast cancer: a phase 1 trial of vandetanib, a VEGFR inhibitor, and metronomic chemotherapy, with correlative platelet proteomics
Mayer EL, Isakoff SJ, Klement G, Downing SR, Chen WY, Hannagan K, Gelman R, Winer EP, Burstein HJ. Combination antiangiogenic therapy in advanced breast cancer: a phase 1 trial of vandetanib, a VEGFR inhibitor, and metronomic chemotherapy, with correlative platelet proteomics. Breast Cancer Research And Treatment 2012, 136: 169-178. PMID: 23001754, PMCID: PMC5472381, DOI: 10.1007/s10549-012-2256-5.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, MetronomicAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, PharmacologicalBlood PlateletsBreast NeoplasmsCombined Modality TherapyCyclophosphamideDrug-Related Side Effects and Adverse ReactionsFemaleGene Expression Regulation, NeoplasticHumansMethotrexateMiddle AgedNeoplasm StagingNeovascularization, PathologicPiperidinesPlatelet Factor 4ProteomicsQuinazolinesVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1ConceptsMetastatic breast cancerBreast cancerMetronomic chemotherapyAntiangiogenic therapyCombination antiangiogenic therapyDose-escalation cohortsPrior chemotherapy regimensResponse-evaluable patientsAdvanced breast cancerModest clinical activityDose-limiting toxicityPhase 1 studyPhase 1 trialVascular endothelial growth factorPlatelet factor 4Platelet-associated proteinsEndothelial growth factorEligible patientsLFT abnormalitiesMetronomic cyclophosphamideStable diseaseChemotherapy regimensPrimary endpointSecondary endpointsPartial responsePhase I, open-label study of olaparib plus cisplatin in patients with advanced solid tumors.
Balmaña J, Tung N, Isakoff S, Graña B, Ryan P, Rafi R, Tracy M, Winer E, Baselga J, Garber J. Phase I, open-label study of olaparib plus cisplatin in patients with advanced solid tumors. Journal Of Clinical Oncology 2012, 30: 1009-1009. DOI: 10.1200/jco.2012.30.15_suppl.1009.Peer-Reviewed Original ResearchAdvanced solid tumorsHematologic AEsEvaluable ptsMonotherapy phaseDose reductionSolid tumorsAntitumor activityOpen-label studyDose-limiting toxicityCisplatin-related toxicityDose-finding studyDrug-related deathsOral PARP inhibitorLong respondersOlaparib capsulesNeoadjuvant settingPrior regimensStable diseaseDurable responsesObjective responsePeritoneal cancerTherapy cyclesMedian numberBreast cancerTreatment cyclesHALT MBC: HER2 suppression with the addition of lapatinib to trastuzumab in HER2-positive metastatic breast cancer (LPT112515).
Lin N, Danso M, David A, Muscato J, Rayson D, Houck W, Ellis C, DeSilvio M, Garofalo A, Nagarwala Y, Winer E. HALT MBC: HER2 suppression with the addition of lapatinib to trastuzumab in HER2-positive metastatic breast cancer (LPT112515). Journal Of Clinical Oncology 2012, 30: tps658-tps658. DOI: 10.1200/jco.2012.30.15_suppl.tps658.Peer-Reviewed Original ResearchHER2-positive metastatic BCSecond-line treatmentMetastatic BCOverall survivalHigher pathologic complete response rateHER2-positive metastatic breast cancerBreast cancer preclinical modelsPathologic complete response rateClinical benefit rateDual HER2 blockadeStable brain metastasesComplete response rateCombination of trastuzumabHormone receptor statusPhase III studyAddition of lapatinibKey eligibility criteriaMetastatic breast cancerLine of treatmentChemotherapy discontinuationHER2 blockadeITT populationMedian PFSStable diseaseBrain metastasesSU2C phase Ib study of pan-PI3K inhibitor BKM120 with letrozole in ER+/HER2- metastatic breast cancer (MBC).
Mayer I, Abramson V, Balko J, Isakoff S, Kuba M, Sanders M, Forero-Torres A, Yap J, Van Den Abbeele A, Li Y, Arteaga C, Winer E. SU2C phase Ib study of pan-PI3K inhibitor BKM120 with letrozole in ER+/HER2- metastatic breast cancer (MBC). Journal Of Clinical Oncology 2012, 30: 510-510. DOI: 10.1200/jco.2012.30.15_suppl.510.Peer-Reviewed Original ResearchMetastatic breast cancerPan-PI3K inhibitor BKM120FDG-PETArm API3K pathway alterationsPhase Ib studyPhase Ib trialPost-menopausal patientsPI3K pathway inhibitionPI3K mutationsPI3K inhibitorsIb trialStable diseaseVisceral metastasesUnacceptable toxicityMost patientsArm BMedian ageDisease progressionPharmacodynamic biomarkersBreast cancerTreatment responseTumor biopsiesAntiestrogen resistanceIb study
2011
P1-17-10: Cabozantinib (XL184) in Patients with Metastatic Breast Cancer: Results from a Phase 2 Randomized Discontinuation Trial.
Tolaney S, Nechushtan H, Berger R, Kurzrock R, Ron I, Schöffski P, Awada A, Yasenchak C, Burris H, Ramies D, Shen X, Winer E. P1-17-10: Cabozantinib (XL184) in Patients with Metastatic Breast Cancer: Results from a Phase 2 Randomized Discontinuation Trial. Cancer Research 2011, 71: p1-17-10-p1-17-10. DOI: 10.1158/0008-5472.sabcs11-p1-17-10.Peer-Reviewed Original ResearchMetastatic breast cancerObjective response rateStable diseasePartial responseBone scanBreast cancerBone metastasesNarcotic useDiscontinuation trialClinical activityWk 12Common related adverse eventsOverall disease control ratePost-baseline tumour assessmentPrior anti-VEGF therapyBone marker analysesFatigue/astheniaPrior treatment regimensPrior treatment statusDisease control rateHand-foot syndromeProgression-free survivalRelated adverse eventsAnti-VEGF therapyInvasive ductal carcinomaOT1-02-02: HALT MBC: HER2 Suppression with the Addition of Lapatinib to Trastuzumab in HER2−Positive Metastatic Breast Cancer (LPT112515).
Lin N, Danso M, David A, Muscato J, Ellis C, DeSilvio M, Garofalo A, Nagarwala Y, Winer E. OT1-02-02: HALT MBC: HER2 Suppression with the Addition of Lapatinib to Trastuzumab in HER2−Positive Metastatic Breast Cancer (LPT112515). Cancer Research 2011, 71: ot1-02-02-ot1-02-02. DOI: 10.1158/0008-5472.sabcs11-ot1-02-02.Peer-Reviewed Original ResearchSecond-line treatmentAddition of lapatinibOverall survivalHigher pathological complete response rateBreast cancer preclinical modelsPathological complete response rateClinical benefit rateDual HER2 blockadeStable brain metastasesComplete response rateHormone receptor statusPhase III studyMetastatic breast cancerLine of treatmentAnti-tumor activityHER2 blockadeMedian PFSStable diseaseBrain metastasesEfficacy endpointMaintenance therapyPreoperative treatmentAdverse eventsHazard ratioIII studyPhase I/II Study of Trastuzumab in Combination With Everolimus (RAD001) in Patients With HER2-Overexpressing Metastatic Breast Cancer Who Progressed on Trastuzumab-Based Therapy
Morrow PK, Wulf GM, Ensor J, Booser DJ, Moore JA, Flores PR, Xiong Y, Zhang S, Krop IE, Winer EP, Kindelberger DW, Coviello J, Sahin AA, Nuñez R, Hortobagyi GN, Yu D, Esteva FJ. Phase I/II Study of Trastuzumab in Combination With Everolimus (RAD001) in Patients With HER2-Overexpressing Metastatic Breast Cancer Who Progressed on Trastuzumab-Based Therapy. Journal Of Clinical Oncology 2011, 29: 3126-3132. PMID: 21730275, PMCID: PMC3157979, DOI: 10.1200/jco.2010.32.2321.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsDisease-Free SurvivalEverolimusFemaleHumansImmunohistochemistryKaplan-Meier EstimateMiddle AgedNeoplasm MetastasisPTEN PhosphohydrolaseReceptor, ErbB-2Salvage TherapySirolimusTOR Serine-Threonine KinasesTrastuzumabConceptsHER2-overexpressing metastatic breast cancerMetastatic breast cancerProgression-free survivalCombination of everolimusTrastuzumab-based therapyPTEN lossBreast cancerPhase I/II studyMedian progression-free survivalDana-Farber Cancer InstituteTexas MD Anderson Cancer CenterMD Anderson Cancer CenterBeth Israel Deaconess Medical CenterClinical benefit ratePersistent stable diseaseAnderson Cancer CenterDownstream mammalian targetDaily everolimusNonhematologic toxicityStable diseaseII studyOverall survivalPartial responseHER2 overexpressingClinical benefit