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 inhibitorOutcomes with trastuzumab deruxtecan (T-DXd) by HER2 status and line of treatment in a large real-world database of patients with metastatic breast cancer.
Tarantino P, Lee D, Foldi J, Soulos P, Gross C, Grinda T, Winer E, Lin N, Krop I, Tolaney S, Lustberg M, Sammons S. Outcomes with trastuzumab deruxtecan (T-DXd) by HER2 status and line of treatment in a large real-world database of patients with metastatic breast cancer. Journal Of Clinical Oncology 2024, 42: 1077-1077. DOI: 10.1200/jco.2024.42.16_suppl.1077.Peer-Reviewed Original ResearchReal-world progression-free survivalLines of therapyMetastatic breast cancerMedian real-world progression-free survivalT-DXdHER2+Overall survivalHER2-lowHER2- patientsBreast cancerHER2- metastatic breast cancerTreat metastatic breast cancerProgression-free survivalKaplan-Meier methodLines of treatmentDatabase of patientsRetrospective observational studyClinical trial settingHER2 casesIHC 0Trastuzumab deruxtecanHR statusHER2 statusTriple-negativeMedian ageTBCRC 048 (olaparib expanded) expansion cohorts: Phase 2 study of olaparib monotherapy in patients (pts) with metastatic breast cancer (MBC) with germline (g) mutations in PALB2 or somatic (s) mutations in BRCA1 or BRCA2.
Tung N, Robson M, Nanda R, Li T, Vinayak S, Shah P, Khoury K, Kimmick G, Santa-Maria C, Brufsky A, DeMeo M, Vieira J, Carey L, Wulf G, Domchek S, Krop I, Wolff A, Winer E, Garber J. TBCRC 048 (olaparib expanded) expansion cohorts: Phase 2 study of olaparib monotherapy in patients (pts) with metastatic breast cancer (MBC) with germline (g) mutations in PALB2 or somatic (s) mutations in BRCA1 or BRCA2. Journal Of Clinical Oncology 2024, 42: 1021-1021. DOI: 10.1200/jco.2024.42.16_suppl.1021.Peer-Reviewed Original ResearchProgression-free survivalDuration of responseMetastatic breast cancerClinical benefit rateTriple-negative breast cancerMedian duration of responseMedian progression-free survivalMutant allele frequencyExpansion cohortHER2-negativeHER2-positiveCohort 2aNon-respondersBreast cancerEarly due to slow enrollmentMetastatic chemotherapy regimensResponse to olaparibPhase 2 studyPhase II trialKaplan-Meier methodPredictors of responseCohort of womenWilcoxon rank sum testRank sum testBRCA1mPooled analysis by best confirmed response to trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2+ metastatic breast cancer (mBC) from DESTINY-Breast-01, -02, and -03.
Cortés J, Modi S, Kim S, Hamilton E, Hurvitz S, Krop I, Curigliano G, Iwata H, Im S, Herbolsheimer P, Karnoub M, Gambhire D, Egorov A, Andre F. Pooled analysis by best confirmed response to trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2+ metastatic breast cancer (mBC) from DESTINY-Breast-01, -02, and -03. Journal Of Clinical Oncology 2024, 42: 1023-1023. DOI: 10.1200/jco.2024.42.16_suppl.1023.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsHER2+ metastatic breast cancerProgression-free survivalMetastatic breast cancerComplete responsePartial responseT-DXdOverall survivalPooled analysisInterstitial lung disease (ILD)/pneumonitisStable disease (SD)/progressive diseaseProlonged progression-free survivalDuration of responseIndependent central reviewNumerically lower ratesLonger treatment durationMetastatic settingRECIST v1.1Trastuzumab deruxtecanOS outcomesCentral reviewAdverse eventsBreast cancerTreatment durationDrug-relatedTrastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): patient-reported outcomes from a randomised, open-label, multicentre, phase 3 trial
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, Egorov A, Kim S. Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): patient-reported outcomes from a randomised, open-label, multicentre, phase 3 trial. The Lancet Oncology 2024, 25: 614-625. PMID: 38697155, DOI: 10.1016/s1470-2045(24)00128-1.Peer-Reviewed Original ResearchConceptsTreatment of physician's choiceMetastatic breast cancerTreatment of physician's choice groupPatient-reported outcomesPhysician's choice groupTrastuzumab deruxtecan groupTrastuzumab deruxtecanPhase 3 trialHER2-positiveBreast cancerGlobal health statusPhysician's choiceEORTC QLQ-C30 global health statusPatient-reported outcome variablesOpen-labelQLQ-C30 global health statusTrastuzumab emtansineDefinitive deteriorationMedian time to definitive deteriorationHER2-positive metastatic breast cancerEastern Cooperative Oncology Group performance statusTreatment durationBlinded independent central reviewQuality of lifeProgression-free survivalDatopotamab Deruxtecan in Advanced or Metastatic HR+/HER2– and Triple-Negative Breast Cancer: Results From the Phase I TROPION-PanTumor01 Study
Bardia A, Krop I, Kogawa T, Juric D, Tolcher A, Hamilton E, Mukohara T, Lisberg A, Shimizu T, Spira A, Tsurutani J, Damodaran S, Papadopoulos K, Greenberg J, Kobayashi F, Zebger-Gong H, Wong R, Kawasaki Y, Nakamura T, Meric-Bernstam F. Datopotamab Deruxtecan in Advanced or Metastatic HR+/HER2– and Triple-Negative Breast Cancer: Results From the Phase I TROPION-PanTumor01 Study. Journal Of Clinical Oncology 2024, 42: 2281-2294. PMID: 38652877, PMCID: PMC11210948, DOI: 10.1200/jco.23.01909.Peer-Reviewed Original ResearchTriple-negative BCHR+/HER2- BCBreast cancerHormone receptor-positive/human epidermal growth factor receptor 2-negativeAll-causality treatment-emergent adverse eventsMedian duration of responseTopoisomerase I inhibitor payloadTreatment-emergent adverse eventsBlinded independent central reviewTriple-negative breast cancerDose-expansion studyProgression-free survivalDuration of responsePhase III studyIndependent central reviewTreating solid tumorsPrimary study objectiveAntibody-drug conjugatesDose escalationData cutoffTriple-negativeBC cohortEvaluation of antitumor activityIII studiesMedian duration
2023
Trastuzumab deruxtecan in previously treated patients with HER2-positive metastatic breast cancer: updated survival results from a phase II trial (DESTINY-Breast01) ☆
Saura C, Modi S, Krop I, Park Y, Kim S, Tamura K, Iwata H, Tsurutani J, Sohn J, Mathias E, Liu Y, Cathcart J, Singh J, Yamashita T. Trastuzumab deruxtecan in previously treated patients with HER2-positive metastatic breast cancer: updated survival results from a phase II trial (DESTINY-Breast01) ☆. Annals Of Oncology 2023, 35: 302-307. PMID: 38092229, DOI: 10.1016/j.annonc.2023.12.001.Peer-Reviewed Original ResearchHER2-positive metastatic breast cancerTreatment-emergent adverse eventsMetastatic breast cancerObjective response rateProgression-free survivalDuration of responseIndependent central reviewT-DXdAdverse eventsOverall survivalTrastuzumab deruxtecanCentral reviewBreast cancerDrug-related treatment-emergent adverse eventsInterstitial lung disease/pneumonitisResponse rateMedian progression-free survivalPositive metastatic breast cancerHuman epidermal growth factor receptor 2End pointEpidermal growth factor receptor 2Sustained antitumor activityAntitumor activityMedian overall survivalPrimary end pointMultiple PIK3CA mutation clonality correlates with outcomes in taselisib + fulvestrant-treated ER+/HER2–, PIK3CA-mutated breast cancers
Hutchinson K, Chen J, Savage H, Stout T, Schimmoller F, Cortés J, Dent S, Harbeck N, Jacot W, Krop I, Trabucco S, Sivakumar S, Sokol E, Wilson T. Multiple PIK3CA mutation clonality correlates with outcomes in taselisib + fulvestrant-treated ER+/HER2–, PIK3CA-mutated breast cancers. Genome Medicine 2023, 15: 28. PMID: 37101291, PMCID: PMC10131374, DOI: 10.1186/s13073-023-01181-8.Peer-Reviewed Original ResearchConceptsPI3K pathwayBreast cancerK pathwayP110α inhibitionLonger progression-free survivalReceptor tyrosine kinasesProgression-free survivalMetastatic breast cancerComprehensive genomic profilingPI3K pathway genesFurther clinical investigationP110α inhibitorsHigh response rateSolid tumor typesBreast cancer tumorsP110α catalytic subunitClinical trialsClinical investigationIndependent cohortImportant molecular determinantResponse rateTumor typesPIK3CA geneConclusionsOur studyTumor DNATrastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial
André F, Hee Park Y, Kim S, Takano T, Im S, Borges G, Lima J, Aksoy S, Gavila Gregori J, De Laurentiis M, Bianchini G, Roylance R, Miyoshi Y, Armstrong A, Sinha R, Ruiz Borrego M, Lim E, Ettl J, Yerushalmi R, Zagouri F, Duhoux F, Fehm T, Gambhire D, Cathcart J, Wu C, Chu C, Egorov A, Krop I. Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial. The Lancet 2023, 401: 1773-1785. PMID: 37086745, DOI: 10.1016/s0140-6736(23)00725-0.Peer-Reviewed Original ResearchConceptsHER2-positive metastatic breast cancerMetastatic breast cancerPhysician's choice groupTreatment-emergent adverse eventsBlinded independent central reviewPhase 3 trialProgression-free survivalTrastuzumab deruxtecanIndependent central reviewBreast cancerPhysician's choiceAdverse eventsCentral reviewTrastuzumab emtansineEastern Cooperative Oncology Group performance statusCommon treatment-emergent adverse eventsHigher treatment-emergent adverse eventsMedian progression-free survivalPositive metastatic breast cancerFavorable benefit-risk profilePalmar-plantar erythrodysaesthesiaInterstitial lung diseaseBenefit-risk profileAntibody-drug conjugatesChoice groupER+, HER2− advanced breast cancer treated with taselisib and fulvestrant: genomic landscape and associated clinical outcomes
Chen J, Jacot W, Cortés J, Krop I, Dent S, Harbeck N, De Laurentiis M, Diéras V, Im Y, Stout T, Schimmoller F, Savage H, Hutchinson K, Wilson T. ER+, HER2− advanced breast cancer treated with taselisib and fulvestrant: genomic landscape and associated clinical outcomes. Molecular Oncology 2023, 17: 2000-2016. PMID: 36892268, PMCID: PMC10552898, DOI: 10.1002/1878-0261.13416.Peer-Reviewed Original ResearchConceptsProgression-free survivalBreast cancerShorter progression-free survivalNeurofibromin 1Advanced breast cancerBreast cancer patientsP53 pathway genesPI3K inhibitorsPI3K inhibitionBaseline ctDNAEndocrine therapyClinical outcomesCancer patientsEstrogen receptorCatalytic subunit alphaTumor DNATaselisibK inhibitorsK inhibitionPI3KOutcomesCancerAlterationsGenomic landscapeProtein p53Tucatinib vs Placebo, Both in Combination With Trastuzumab and Capecitabine, for Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer in Patients With Brain Metastases
Lin N, Murthy R, Abramson V, Anders C, Bachelot T, Bedard P, Borges V, Cameron D, Carey L, Chien A, Curigliano G, DiGiovanna M, Gelmon K, Hortobagyi G, Hurvitz S, Krop I, Loi S, Loibl S, Mueller V, Oliveira M, Paplomata E, Pegram M, Slamon D, Zelnak A, Ramos J, Feng W, Winer E. Tucatinib vs Placebo, Both in Combination With Trastuzumab and Capecitabine, for Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer in Patients With Brain Metastases. JAMA Oncology 2023, 9: 197-205. PMID: 36454580, PMCID: PMC9716438, DOI: 10.1001/jamaoncol.2022.5610.Peer-Reviewed Original ResearchConceptsErbB2-positive metastatic breast cancerMetastatic breast cancerPlacebo-combination groupPositive metastatic breast cancerNew brain lesionsBrain metastasesOverall survivalSubgroup analysisBrain lesionsBreast cancerIntracranial progression-free survivalPlacebo-controlled clinical trialIntracranial objective response rateStable brain metastasesMedian overall survivalObjective response rateProgression-free survivalExploratory subgroup analysisGreater clinical benefitCNS-PFSHER2CLIMB trialIntracranial outcomesFirst progressionMedian ageClinical benefit
2022
Trastuzumab Deruxtecan in HER2-Positive Metastatic Breast Cancer Patients with Brain Metastases: A DESTINY-Breast01 Subgroup Analysis
Jerusalem G, Park YH, Yamashita T, Hurvitz S, Modi S, Andre F, Krop I, Farré X, You B, Saura C, Kim S, Osborne C, Murthy R, Gianni L, Takano T, Liu Y, Cathcart J, Lee C, Perrin C. Trastuzumab Deruxtecan in HER2-Positive Metastatic Breast Cancer Patients with Brain Metastases: A DESTINY-Breast01 Subgroup Analysis. Cancer Discovery 2022, 12: 2754-2762. PMID: 36255231, PMCID: PMC9716244, DOI: 10.1158/2159-8290.cd-22-0837.Peer-Reviewed Original ResearchConceptsMedian progression-free survivalMetastatic breast cancerHER2-positive metastatic breast cancerBrain metastasesT-DXdTrastuzumab deruxtecanBreast cancerHER2-positive metastatic breast cancer patientsMetastatic breast cancer patientsDurable clinical activityObjective response rateProgression-free survivalBreast cancer patientsLimited treatment optionsPopulation warrants further investigationBest percentage changeWarrants further investigationIntracranial progressionStable diseasePartial responseComplete responseDurable efficacySafety profileTherapeutic optionsTreatment optionsPhase 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 blockadeClinical Efficacy and Whole-Exome Sequencing of Liquid Biopsies in a Phase IB/II Study of Bazedoxifene and Palbociclib in Advanced Hormone Receptor-Positive Breast Cancer.
Tsuji J, Li T, Grinshpun A, Coorens T, Russo D, Anderson L, Rees R, Nardone A, Patterson C, Lennon NJ, Cibulskis C, Leshchiner I, Tayob N, Tolaney SM, Tung N, McDonnell DP, Krop IE, Winer EP, Stewart C, Getz G, Jeselsohn R. Clinical Efficacy and Whole-Exome Sequencing of Liquid Biopsies in a Phase IB/II Study of Bazedoxifene and Palbociclib in Advanced Hormone Receptor-Positive Breast Cancer. Clinical Cancer Research 2022, 28: 5066-5078. PMID: 36215125, PMCID: PMC9722539, DOI: 10.1158/1078-0432.ccr-22-2305.Peer-Reviewed Original ResearchConceptsProgression-free survivalPhase Ib/II studyCombination of palbociclibBreast cancerWhole-exome sequencingESR1 mutationsII studyClinical efficacySafety profileHormone receptor-positive/HER2-negative advanced breast cancerAdvanced hormone receptor-positive breast cancerHER2-negative advanced breast cancerHormone receptor-positive breast cancerThird-generation selective estrogen receptor modulatorMedian progression-free survivalEndocrine-resistant breast cancerReceptor-positive breast cancerShorter progression-free survivalSelective estrogen receptor modulatorsClinical benefit rateAcceptable safety profileAdvanced breast cancerEstrogen receptor modulatorsSelective ER degraderDNA whole-exome sequencingClinical outcomes with alpelisib (ALP) plus fulvestrant (FUL) after prior treatment (tx) with FUL in patients (pts) with advanced breast cancer (ABC): A real-world (RW) analysis.
O'Shaughnessy J, Woeckel A, Pistilli B, Hegg R, Vahdat L, Vuina D, Asad ZVK P, Smith T, Kim J, Krop I. Clinical outcomes with alpelisib (ALP) plus fulvestrant (FUL) after prior treatment (tx) with FUL in patients (pts) with advanced breast cancer (ABC): A real-world (RW) analysis. Journal Of Clinical Oncology 2022, 40: 1055-1055. DOI: 10.1200/jco.2022.40.16_suppl.1055.Peer-Reviewed Original ResearchAdvanced breast cancerEndocrine-based therapyPIK3CA mutationsMetastatic settingClinical outcomesCyclin-dependent kinase 4/6 inhibitorsDe-identified electronic health record dataHuman epidermal growth factor receptorImmediate prior therapyLines of therapyProgression-free survivalProgression/deathElectronic health record dataDate of deathHealth record dataEpidermal growth factor receptorReal-world analysisGrowth factor receptorNCCN guidelinesPrior chemotherapyPrior therapyMedian durationMedian timeSubsequent therapyClinical benefitPhase 2 trial of tucatinib plus trastuzumab deruxtecan in patients with HER2+ locally advanced or metastatic breast cancer with and without brain metastases (HER2CLIMB-04, trial in progress).
Krop I, Carey L, Ramos J, Chen Y, Hamilton E. Phase 2 trial of tucatinib plus trastuzumab deruxtecan in patients with HER2+ locally advanced or metastatic breast cancer with and without brain metastases (HER2CLIMB-04, trial in progress). Journal Of Clinical Oncology 2022, 40: tps1111-tps1111. DOI: 10.1200/jco.2022.40.16_suppl.tps1111.Peer-Reviewed Original ResearchHuman epidermal growth factor receptor 2Metastatic breast cancerDisease control rateProgression-free survivalDuration of responseBrain metastasesAntibody-drug conjugatesRECIST 1.1Trastuzumab deruxtecanInvestigator assessmentBreast cancerSmall molecule tyrosine kinase inhibitorsTopoisomerase I inhibitor payloadEpidermal growth factor receptor 2Monoclonal antibodiesBreast cancer xenograft modelActive brain metastasesResponse-evaluable patientsManageable safety profileObjective response ratePhase 2 studyPhase 2 trialGrowth factor receptor 2Limited treatment optionsPatient-reported outcomesManagement of Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases: ASCO Guideline Update
Ramakrishna N, Anders CK, Lin NU, Morikawa A, Temin S, Chandarlapaty S, Crews JR, Davidson NE, Franzoi MAB, Kirshner JJ, Krop IE, Patt DA, Perlmutter J, Giordano SH. Management of Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases: ASCO Guideline Update. Journal Of Clinical Oncology 2022, 40: 2636-2655. PMID: 35640075, DOI: 10.1200/jco.22.00520.Peer-Reviewed Original ResearchConceptsWhole brain radiotherapyAdvanced breast cancerBrain metastasesSystemic therapyBreast cancerLocal therapyGuideline recommendationsAdvanced human epidermal growth factor receptorHER2-positive advanced breast cancerPositive advanced breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Human epidermal growth factor receptorAppropriate local therapyASCO Guideline UpdateBest supportive careProgression-free survivalSize of metastasesGrowth factor receptor 2Presence of symptomsRoutine magnetic resonanceFactor receptor 2Outcomes of interestMagnetic resonance imagingEpidermal growth factor receptorPhase II Study of Taselisib in PIK3CA-Mutated Solid Tumors Other Than Breast and Squamous Lung Cancer: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol I
Krop IE, Jegede OA, Grilley-Olson JE, Lauring JD, Mitchell EP, Zwiebel JA, Gray RJ, Wang V, McShane LM, Rubinstein LV, Patton D, Williams PM, Hamilton SR, Kono SA, Ford JM, Garcia AA, Sui XD, Siegel RD, Slomovitz BM, Conley BA, Arteaga CL, Harris LN, O'Dwyer PJ, Chen AP, Flaherty KT. Phase II Study of Taselisib in PIK3CA-Mutated Solid Tumors Other Than Breast and Squamous Lung Cancer: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol I. JCO Precision Oncology 2022, 6: e2100424. PMID: 35138919, PMCID: PMC8865530, DOI: 10.1200/po.21.00424.Peer-Reviewed Original ResearchConceptsProgression-free survivalOverall survivalSix-month progression-free survivalSolid tumorsMedian progression-free survivalSix-month overall survivalEnd pointSquamous cell lung carcinomaNational Cancer Institute-Molecular AnalysisMedian overall survivalObjective response ratePhase II studyPrimary end pointSecondary end pointsCell lung carcinomaSquamous lung cancerMutant breast cancerCommon toxicitiesEligible patientsProtocol therapyUnacceptable toxicityII studyPartial responseAdvanced cancerClinical outcomes
2021
Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis
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. Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis. Annals Of Oncology 2021, 33: 321-329. PMID: 34954044, DOI: 10.1016/j.annonc.2021.12.005.Peer-Reviewed Original ResearchConceptsProgression-free survivalMetastatic breast cancerPlacebo-combination groupOverall survivalCombination groupBreast cancerHER2CLIMB trialBrain metastasesMedian durationSafety outcomesPrimary analysisFinal overall survival analysisHuman epidermal growth factor receptor 2 positive metastatic breast cancerPositive metastatic breast cancerMeaningful survival benefitMedian overall survivalPlacebo-controlled trialOverall study populationOverall survival analysisFinal OSMetastatic HER2Placebo combinationAdverse eventsLast patientPrespecified subgroupsCirculating tumor cell number and endocrine therapy index in ER positive metastatic breast cancer patients
Paoletti C, Regan MM, Niman SM, Dolce EM, Darga EP, Liu MC, Marcom PK, Hart LL, Smith JW, Tedesco KL, Amir E, Krop IE, DeMichele AM, Goodwin PJ, Block M, Aung K, Brown ME, McCormack RT, Hayes DF. Circulating tumor cell number and endocrine therapy index in ER positive metastatic breast cancer patients. Npj Breast Cancer 2021, 7: 77. PMID: 34117261, PMCID: PMC8196036, DOI: 10.1038/s41523-021-00281-1.Peer-Reviewed Original ResearchMetastatic breast cancerProgression-free survivalER-positive metastatic breast cancerHER2-negative metastatic breast cancerWorse progression-free survivalWhole bloodTherapy indexExact testPositive metastatic breast cancer patientsMedian progression-free survivalMetastatic breast cancer patientsHuman epidermal growth factor receptorMulti-institutional clinical trialsGroup of patientsBreast cancer patientsSerial time pointsFisher's exact testTumor cell numberEpidermal growth factor receptorElevated CTCsGrowth factor receptorPrimary endpointClinical outcomesCancer patientsClinical trials