Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial
| Autor: | Rashmi Krishna Murthy, Amelia Zelnak, Giuseppe Curigliano, Carey K. Anders, Elisavet Paplomata, Mafalda Oliveira, Eric P. Winer, Virginia F. Borges, Karen A. Gelmon, Alison Conlin, Xuebei An, Michael DiGiovanna, Sibylle Loibl, Alicia Okines, Sara A. Hurvitz, Ruth O'Regan, Philippe L. Bedard, Andrew M Wardley, Lisa A. Carey, Thomas Bachelot, Jo Al Mayor, David Cameron, A. Jo Chien, Nan Lin, Sherene Loi, Vandana G. Abramson, Suzanne McGoldrick, Erika Hamilton, Volkmar Mueller |
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| Přispěvatelé: | Institut Català de la Salut, [Lin NU] Dana-Farber Cancer Institute, Boston, MA, USA. [Borges V] University of Colorado Cancer Center, Aurora, CO, USA. [Anders C] Duke Cancer Institute, Durham, NC, USA. [Murthy RK] MD Anderson Cancer Center, Houston, TX, USA. [Paplomata E] Carbone Cancer Center/University of Wisconsin, Madison, WI, USA. [Hamilton E] Sarah Cannon Research Institute/Tennessee Oncology–Nashville, Nashville, TN, USA. [Oliveira M] Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research Pyridines Receptor ErbB-2 medicine.medical_treatment Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES] law.invention ErbB-2 0302 clinical medicine Randomized controlled trial Mama - Càncer law Trastuzumab Antineoplastic Combined Chemotherapy Protocols Other subheadings::/therapeutic use [Other subheadings] Young adult Oxazoles Cancer neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES] Brain Neoplasms Middle Aged 6.1 Pharmaceuticals 030220 oncology & carcinogenesis Disease Progression Female Receptor medicine.drug Adult medicine.medical_specialty Clinical Trials and Supportive Activities Clinical Sciences Oncology and Carcinogenesis Breast Neoplasms Capecitabine 03 medical and health sciences Young Adult Breast cancer Double-Blind Method Clinical Research Internal medicine RAPID COMMUNICATIONS Breast Cancer medicine Humans Oncology & Carcinogenesis terapéutica::protocolos clínicos::protocolos antineoplásicos::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] Aged Medicaments antineoplàstics - Ús terapèutic - Eficàcia business.industry Otros calificadores::/uso terapéutico [Otros calificadores] Neurosciences Evaluation of treatments and therapeutic interventions Therapeutics::Clinical Protocols::Antineoplastic Protocols::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] medicine.disease Radiation therapy 030104 developmental biology Clinical research Quinazolines business |
| Zdroj: | Journal of Clinical Oncology Scientia Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol 38, iss 23 Lin, N U, Borges, V, Anders, C, Murthy, R K, Paplomata, E, Hamilton, E, Hurvitz, S, Loi, S, Okines, A, Abramson, V, Bedard, P L, Oliveira, M, Mueller, V, Zelnak, A, Digiovanna, M P, Bachelot, T, Chien, A J, O’regan, R, Wardley, A, Conlin, A, Cameron, D, Carey, L, Curigliano, G, Gelmon, K, Loibl, S, Mayor, J, Mcgoldrick, S, An, X & Winer, E P 2020, ' Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial ', Journal of Clinical Oncology, pp. JCO.20.00775 . https://doi.org/10.1200/JCO.20.00775, https://doi.org/10.1200/JCO.20.00775 BASE-Bielefeld Academic Search Engine |
| ISSN: | 1527-7755 0732-183X |
| Popis: | PURPOSE In the HER2CLIMB study, patients with human epidermal growth factor receptor 2 (HER2)–positive breast cancer with brain metastases (BMs) showed statistically significant improvement in progression-free survival (PFS) with tucatinib. We describe exploratory analyses of intracranial efficacy and survival in participants with BMs. PATIENTS AND METHODS Patients were randomly assigned 2:1 to tucatinib or placebo, in combination with trastuzumab and capecitabine. All patients underwent baseline brain magnetic resonance imaging; those with BMs were classified as active or stable. Efficacy analyses were performed by applying RECIST 1.1 criteria to CNS target lesions by investigator assessment. CNS-PFS (intracranial progression or death) and overall survival (OS) were evaluated in all patients with BMs. Confirmed intracranial objective response rate (ORR-IC) was evaluated in patients with measurable intracranial disease. RESULTS There were 291 patients with BMs: 198 (48%) in the tucatinib arm and 93 (46%) in the control arm. The risk of intracranial progression or death was reduced by 68% in the tucatinib arm (hazard ratio [HR], 0.32; 95% CI, 0.22 to 0.48; P < .0001). Median CNS-PFS was 9.9 months in the tucatinib arm versus 4.2 months in the control arm. Risk of death was reduced by 42% in the tucatinib arm (OS HR, 0.58; 95% CI, 0.40 to 0.85; P = .005). Median OS was 18.1 versus 12.0 months. ORR-IC was higher in the tucatinib arm (47.3%; 95% CI, 33.7% to 61.2%) versus the control arm (20.0%; 95% CI, 5.7% to 43.7%; P = .03). CONCLUSION In patients with HER2-positive breast cancer with BMs, the addition of tucatinib to trastuzumab and capecitabine doubled ORR-IC, reduced risk of intracranial progression or death by two thirds, and reduced risk of death by nearly half. To our knowledge, this is the first regimen to demonstrate improved antitumor activity against BMs in patients with HER2-positive breast cancer in a randomized, controlled trial. |
| Databáze: | OpenAIRE |
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