title: Health-related quality of life in patients with locally recurrent or metastatic breast cancer treated with etirinotecan pegol versus treatment of physician's choice: Results from the randomised phase III BEACON trial.
abstract: Health-related quality of life (HRQoL) enhances understanding of treatment effects that impact clinical decision-making. Although the primary end-point was not achieved, the BEACON (BrEAst Cancer Outcomes with NKTR-102) trial established etirinotecan pegol, a long-acting topoisomerase-1 (TOP1) inhibitor, as a promising therapeutic for patients with advanced/metastatic breast cancer (MBC) achieving clinically meaningful benefits in median overall survival (OS) for patients with stable brain metastases, with liver metastases or ≥ 2 sites of metastatic disease compared to treatment of physician's choice (TPC). Reported herein are the findings from the preplanned secondary end-point of HRQoL.
  
  
  
  HRQoL, assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) (version 3.0) supplemented by the breast cancer-specific Quality of Life Questionnaire (QLQ-BR23), was evaluated post randomisation in 733 of 852 patients with either anthracycline-, taxane- and capecitabine-pretreated locally recurrent or MBC randomised to etirinotecan pegol (n = 378; 145 mg/m2every 3 weeks (q3wk)) or single-agent TPC (n = 355). Patients completed assessments at screening, every 8 weeks (q8wk) during treatment, and end-of-treatment. Changes from baseline were analysed, and the proportions of patients achieving differences (≥5 points) in HRQoL scores were compared.
  
  
  
  Differences were seen favouring etirinotecan pegol up to 32 weeks for global health status (GHS) and physical functioning scales (P < 0.02); numerical improvement was reported in other functional scales. The findings from HRQoL symptom scales were consistent with adverse event profiles; etirinotecan pegol was associated with worsening gastrointestinal symptoms whereas TPC was associated with worsened dyspnoea and other systemic side-effects. Analysis of GHS and physical functioning at disease progression showed a decline in HRQoL in both treatment arms, with a mean change from baseline of -9.4 and -10.8 points, respectively.
  
  
  
  There was evidence of benefit associated with etirinotecan pegol compared with current standard of care agents in multiple HRQoL measurements, including global health status and physical functioning, despite worse gastrointestinal symptoms (e.g. diarrhoea). Patients in both arms had a decline in HRQoL at disease progression.
  
  
  
  NCT01492101.
authors.affiliation: Leeds Institute of Cancer and Pathology and St James's Institute of Oncology, Leeds, UK. Electronic address: c.j.twelves@leeds.ac.uk.
authors.forename: Chris
authors.initials: C
authors.lastname: Twelves
authors.affiliation: Ramon y Cajal University Hospital, Madrid, Spain; Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Cortés
authors.affiliation: Baylor-Sammons Cancer Center, Texas Oncology, U.S. Oncology, Dallas, TX, USA.
authors.forename: Joyce
authors.initials: J
authors.lastname: O'Shaughnessy
authors.affiliation: Medical Oncology Clinic, Jules Bordet Institute, Brussels, Belgium.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Awada
authors.affiliation: Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.affiliation: Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
authors.affiliation: Vall d'Hebron Institute of Oncology, Barcelona, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Gómez-Pardo
authors.affiliation: The West Clinic, Memphis, TN, USA.
authors.forename: Lee S
authors.initials: LS
authors.lastname: Schwartzberg
authors.affiliation: Institut Curie, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Diéras
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN, USA.
authors.forename: Denise A
authors.initials: DA
authors.lastname: Yardley
authors.affiliation: University of Minnesota, Department of Medicine, Masonic Cancer Center, Minneapolis, MN, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Potter
authors.affiliation: Centre Oscar Lambret, Lille, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Mailliez
authors.affiliation: Ramon y Cajal University Hospital, Madrid, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Moreno-Aspitia
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Jin-Seok
authors.initials: JS
authors.lastname: Ahn
authors.affiliation: Nektar Therapeutics, San Francisco, CA, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Nektar Therapeutics, San Francisco, CA, USA.
authors.forename: Ute
authors.initials: U
authors.lastname: Hoch
authors.affiliation: Nektar Therapeutics, San Francisco, CA, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Tagliaferri
authors.affiliation: Consultant, Sebastopol, CA, USA.
authors.forename: Alison L
authors.initials: AL
authors.lastname: Hannah
authors.affiliation: University of California, San Francisco, CA, USA.
authors.forename: Hope S
authors.initials: HS
authors.lastname: Rugo
mesh_terms: D000203:Activities of Daily Living; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000418:Albumins / Q000627:therapeutic use; D000855:Anorexia; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001828:Body Image; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000072716:Cancer Pain; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077143:Docetaxel; D004417:Dyspnea; D034261:Epothilones / Q000627:therapeutic use; D005221:Fatigue; D005260:Female; D005663:Furans / Q000627:therapeutic use; D006304:Health Status; D006576:Heterocyclic Compounds, 4 or More Rings / Q000627:therapeutic use*; D006801:Humans; D007659:Ketones / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D009325:Nausea; D017239:Paclitaxel / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011788:Quality of Life; D060728:Reproductive Health; D007319:Sleep Initiation and Maintenance Disorders; D043823:Taxoids / Q000627:therapeutic use; D014747:Vinblastine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077235:Vinorelbine; D014839:Vomiting; D000093542:Gemcitabine; D000095662:Polyether Polyketides
chemical_list: D000418:Albumins; D000970:Antineoplastic Agents; D003841:Deoxycytidine; D000077143:Docetaxel; D034261:Epothilones; D005663:Furans; D006576:Heterocyclic Compounds, 4 or More Rings; D007659:Ketones; D017239:Paclitaxel; D011092:Polyethylene Glycols; D043823:Taxoids; D014747:Vinblastine; D000077235:Vinorelbine; D000093542:Gemcitabine; C520255:130-nm albumin-bound paclitaxel; C430592:ixabepilone; C581703:etirinotecan pegol; C490954:eribulin; D000095662:Polyether Polyketides
keywords: Advanced breast cancer; Etirinotecan pegol; Metastatic breast cancer; NKTR-102; Quality of life