Sistema de Salut de Catalunya
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
2021-08-23T09:56:40Z
2021-08-23T09:56:40Z
2020-08-10
Càncer de mama; Supervivència; Tucatinib
Cáncer de mama; Supervivencia; Tucatinib
Breast cancer; Survival; Tucatinib
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.
Article
Published version
English
Mama - Càncer; Medicaments antineoplàstics - Ús terapèutic - Eficàcia; DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Clinical Protocols::Antineoplastic Protocols::Antineoplastic Combined Chemotherapy Protocols; Other subheadings::Other subheadings::/therapeutic use; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::protocolos clínicos::protocolos antineoplásicos::protocolos de quimioterapia antineoplásica combinada; Otros calificadores::Otros calificadores::/uso terapéutico
American Society of Clinical Oncology
Journal of Clinical Oncology;38(23)
https://ascopubs.org/doi/10.1200/JCO.20.00775
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
Articles científics - HVH [3439]
