2023
Tucatinib 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
2013
Human epidermal growth factor receptor 2 (HER2) suppression with the addition of lapatinib to trastuzumab in HER2-positive metastatic breast cancer (HALT: LPT112515).
Lin N, Danso M, David A, Muscato J, Rayson D, Houck W, Ellis C, DeSilvio M, Garofalo A, Levin J, Winer E. Human epidermal growth factor receptor 2 (HER2) suppression with the addition of lapatinib to trastuzumab in HER2-positive metastatic breast cancer (HALT: LPT112515). Journal Of Clinical Oncology 2013, 31: tps664-tps664. DOI: 10.1200/jco.2013.31.15_suppl.tps664.Peer-Reviewed Original ResearchProgression-free survivalMetastatic breast cancerBreast cancerOverall survivalMetastatic BCPFS eventsStage II/III breast cancerHigher pathologic complete response rateHER2-positive metastatic breast cancerMedian progression-free survivalPathologic complete response rateLonger progression-free survivalAssociated hazard ratiosClinical benefit rateDual HER2 blockadeStable brain metastasesComplete response rateSecond-line treatmentHormone receptor statusPhase III studyAddition of lapatinibLine of treatmentChemotherapy discontinuationEligible patientsHER2 blockade
2012
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, 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 metastases
2011
OT1-02-02: 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 study
2009
A phase I study of vandetanib and metronomic chemotherapy in advanced breast cancer.
Mayer E, Isakoff S, Hannagan K, Savoie J, Beckman J, Klement G, Gelman R, Winer E, Burstein H. A phase I study of vandetanib and metronomic chemotherapy in advanced breast cancer. Cancer Research 2009, 69: 906. DOI: 10.1158/0008-5472.sabcs-906.Peer-Reviewed Original ResearchAdvanced breast cancerDose-escalation cohortsAbnormal hepatic functionVascular endothelial growth factorBreast cancerMetronomic chemotherapyHepatic functionContinuous low-dose oral cyclophosphamideLow-dose oral cyclophosphamideSequential dose-escalation cohortsStage IV breast cancerOral tyrosine kinase inhibitorGrade 3 eventsOral combination therapyPrior chemotherapy regimensStable brain metastasesModest clinical activityAnti-angiogenic treatmentTyrosine kinase inhibitorsEndothelial growth factorEpidermal growth factor receptorEligible patientsGrowth factor receptorMeasurable diseaseModerate hypertension