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
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 subgroups
2019
Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer
Murthy RK, Loi S, Okines A, Paplomata E, Hamilton E, Hurvitz SA, Lin NU, Borges V, Abramson V, Anders C, Bedard PL, Oliveira M, Jakobsen E, Bachelot T, Shachar SS, Müller V, Braga S, Duhoux FP, Greil R, Cameron D, Carey LA, Curigliano G, Gelmon K, Hortobagyi G, Krop I, Loibl S, Pegram M, Slamon D, Palanca-Wessels MC, Walker L, Feng W, Winer EP. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. New England Journal Of Medicine 2019, 382: 597-609. PMID: 31825569, DOI: 10.1056/nejmoa1914609.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsBrain NeoplasmsBreast NeoplasmsCapecitabineConsolidation ChemotherapyDiarrheaDouble-Blind MethodFemaleHumansKaplan-Meier EstimateMiddle AgedOxazolesProgression-Free SurvivalProtein-Tyrosine KinasesPyridinesQuinazolinesReceptor, ErbB-2TrastuzumabConceptsHER2-positive metastatic breast cancerProgression-free survivalPlacebo-combination groupMetastatic breast cancerElevated aminotransferase levelsBrain metastasesBreast cancerOverall survivalAminotransferase levelsMedian progression-free survivalPalmar-plantar erythrodysesthesia syndromeBetter progression-free survivalPositive metastatic breast cancerHuman epidermal growth factor receptor 2End pointEpidermal growth factor receptor 2Common adverse eventsMedian overall survivalObjective response ratePrimary end pointSecondary end pointsGrowth factor receptor 2Overall survival outcomesRisk of diarrheaFactor receptor 2
2018
369TiP PATINA: A randomized, open label, phase III trial to evaluate the efficacy and safety of palbociclib + Anti-HER2 therapy + endocrine therapy (ET) vs. anti-HER2 therapy + ET after induction treatment for hormone receptor positive (HR+)/HER2-positive metastatic breast cancer (MBC)
Loibl S, Metzger O, Mandrekar S, Mundhenke C, Seiler S, Valagussa P, DeMichele A, Lim E, Tripathy D, Winer E, Huang C, Carey L, Francis P, Miller K, Goetz M, Prat A, Loi S, Krop I, Gianni L, Ciruelos E. 369TiP PATINA: A randomized, open label, phase III trial to evaluate the efficacy and safety of palbociclib + Anti-HER2 therapy + endocrine therapy (ET) vs. anti-HER2 therapy + ET after induction treatment for hormone receptor positive (HR+)/HER2-positive metastatic breast cancer (MBC). Annals Of Oncology 2018, 29: viii121. DOI: 10.1093/annonc/mdy272.357.Peer-Reviewed Original ResearchWhole exome sequencing (WES) in hormone-receptor positive (HR+) metastatic breast cancer (MBC) to identify mediators of resistance to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i).
Wander S, Cohen O, Johnson G, Kim D, Luo F, Mao P, Nayar U, Helvie K, Marini L, Freeman S, Getz G, Garraway L, Winer E, Lin N, Wagle N. Whole exome sequencing (WES) in hormone-receptor positive (HR+) metastatic breast cancer (MBC) to identify mediators of resistance to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). Journal Of Clinical Oncology 2018, 36: 12016-12016. DOI: 10.1200/jco.2018.36.15_suppl.12016.Peer-Reviewed Original Research
2011
Responses to subsequent anti-HER2 therapy after treatment with trastuzumab-DM1 in women with HER2-positive metastatic breast cancer
Olson EM, Lin NU, DiPiro PJ, Najita JS, Krop IE, Winer EP, Burstein HJ. Responses to subsequent anti-HER2 therapy after treatment with trastuzumab-DM1 in women with HER2-positive metastatic breast cancer. Annals Of Oncology 2011, 23: 93-97. PMID: 21531783, PMCID: PMC3276325, DOI: 10.1093/annonc/mdr061.Peer-Reviewed Original ResearchConceptsAnti-HER2 therapyMetastatic breast cancerHER2-positive MBC patientsT-DM1MBC patientsBreast cancerHER2-positive metastatic breast cancerSingle-agent T-DM1Positive metastatic breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Blinded radiology reviewAnti-HER2 agentsGrowth factor receptor 2Kaplan-Meier estimatesFurther clinical benefitFactor receptor 2Protocol therapyMedian durationFurther therapyPartial responseRadiology reviewClinical benefitSubsequent linesMetastatic therapy