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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorTurner, N. C.
dc.contributor.authorAlarcón, E.
dc.contributor.authorArmstrong, A. C.
dc.contributor.authorPhilco, M.
dc.contributor.authorLópez Chuken, Y. A.
dc.contributor.authorSablin, Marie-Paule
dc.contributor.authorAntunes de Melo Oliveira, Ana Mafalda
dc.date.accessioned2021-03-16T09:36:56Z
dc.date.available2021-03-16T09:36:56Z
dc.date.issued2019-05-01
dc.identifier.citationTurner NC, Alarcón E, Armstrong AC, Philco M, López Chuken YA, Sablin MP, et al. BEECH: A dose-finding run-in followed by a randomised phase II study assessing the efficacy of AKT inhibitor capivasertib (AZD5363) combined with paclitaxel in patients with estrogen receptor-positive advanced or metastatic breast cancer, and in a PIK3CA. Ann Oncol. 2019 May 1;30(5):774–80.
dc.identifier.issn1569-8041
dc.identifier.urihttp://hdl.handle.net/11351/5759
dc.descriptionAKT inhibitor; PIK3CA; Capivasertib
dc.description.abstractBackground BEECH investigated the efficacy of capivasertib (AZD5363), an oral inhibitor of AKT isoforms 1–3, in combination with the first-line weekly paclitaxel for advanced or metastatic estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancer, and in a phosphoinositide 3-kinase, catalytic, alpha polypeptide mutation sub-population (PIK3CA+). Patients and methods BEECH consisted of an open-label, phase Ib safety run-in (part A) in 38 patients with advanced breast cancer, and a randomised, placebo-controlled, double-blind, phase II expansion (part B) in 110 women with ER+/HER2− metastatic breast cancer. In part A, patients received paclitaxel 90 mg/m2 (days 1, 8 and 15 of a 28-day cycle) with capivasertib taken twice daily (b.i.d.) at two intermittent ascending dosing schedules. In part B, patients were randomly assigned, stratified by PIK3CA mutation status, to receive paclitaxel with either capivasertib or placebo. The primary end point for part A was safety to recommend a dose and schedule for part B; primary end points for part B were progression-free survival (PFS) in the overall and PIK3CA+ sub-population. Results Capivasertib was well tolerated, with a 400 mg b.i.d. 4 days on/3 days off treatment schedule selected in part A. In part B, median PFS in the overall population was 10.9 months with capivasertib versus 8.4 months with placebo [hazard ratio (HR) 0.80; P = 0.308]. In the PIK3CA+ sub-population, median PFS was 10.9 months with capivasertib versus 10.8 months with placebo (HR 1.11; P = 0.760). Based on the Common Terminology Criteria for Adverse Event v4.0, the most common grade ≥3 adverse events in the capivasertib group were diarrhoea, hyperglycaemia, neutropoenia and maculopapular rash. Dose intensity of paclitaxel was similar in both groups. Conclusions Capivasertib had no apparent impact on the tolerability and dose intensity of paclitaxel. Adding capivasertib to weekly paclitaxel did not prolong PFS in the overall population or PIK3CA+ sub-population of ER+/HER2− advanced/metastatic breast cancer patients.
dc.language.isoeng
dc.publisherOxford University Press
dc.relation.ispartofseriesAnnals of Oncology;30(5)
dc.rightsAttribution-NonCommercial 4.0 International
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.sourceScientia
dc.subjectEstrògens - Receptors
dc.subjectMetàstasi
dc.subjectMama - Càncer - Tractament
dc.subject.meshNeoplasm Metastasis
dc.subject.meshBreast Neoplasms
dc.subject.mesh/drug therapy
dc.subject.meshReceptors, Estrogen
dc.titleBEECH: a dose-finding run-in followed by a randomised phase II study assessing the efficacy of AKT inhibitor capivasertib (AZD5363) combined with paclitaxel in patients with estrogen receptor-positive advanced or metastatic breast cancer, and in a PIK3CA mutant sub-population
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1093/annonc/mdz086
dc.subject.decsmetástasis neoplásica
dc.subject.decsneoplasias de la mama
dc.subject.decs/farmacoterapia
dc.subject.decsreceptores de estrógenos
dc.relation.publishversionhttps://www.annalsofoncology.org/article/S0923-7534(19)31171-8/fulltext
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Turner NC] Breast Unit, The Royal Marsden NHS Foundation Trust, London, UK. Breast Cancer Now Research Centre, The Institute of Cancer Research, London, UK. [Alarcón E] Clinical Oncology Department, British American Hospital, Lima, Peru. [Armstrong AC] Department of Medical Oncology, Christie Hospital NHS Foundation Trust and Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. [Philco M] Peruvian Institute of Oncology Radiotherapy, Lima, Peru. [López Chuken YA] University Hospital, Monterrey, Mexico. [Sablin MP] Department of Drug Development and Innovation (D3i), Curie Institute, Paris, France. [Oliveira, M] Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
dc.identifier.pmid30860570
dc.identifier.wos000482490300013
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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