Chris Twelves1, Javier Cortés2, Joyce O'Shaughnessy3, Ahmad Awada4, Edith A Perez5, Seock-Ah Im6, Patricia Gómez-Pardo7, Lee S Schwartzberg8, Véronique Diéras9, Denise A Yardley10, David A Potter11, Audrey Mailliez12, Alvaro Moreno-Aspitia13, Jin-Seok Ahn14, Carol Zhao15, Ute Hoch15, Mary Tagliaferri15, Alison L Hannah16, Hope S Rugo17. 1. Leeds Institute of Cancer and Pathology and St James's Institute of Oncology, Leeds, UK. Electronic address: c.j.twelves@leeds.ac.uk. 2. Ramon y Cajal University Hospital, Madrid, Spain; Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. 3. Baylor-Sammons Cancer Center, Texas Oncology, U.S. Oncology, Dallas, TX, USA. 4. Medical Oncology Clinic, Jules Bordet Institute, Brussels, Belgium. 5. Mayo Clinic, Jacksonville, FL, USA. 6. Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. 7. Vall d'Hebron Institute of Oncology, Barcelona, Spain. 8. The West Clinic, Memphis, TN, USA. 9. Institut Curie, Paris, France. 10. Sarah Cannon Research Institute, Nashville, TN, USA. 11. University of Minnesota, Department of Medicine, Masonic Cancer Center, Minneapolis, MN, USA. 12. Centre Oscar Lambret, Lille, France. 13. Ramon y Cajal University Hospital, Madrid, Spain. 14. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. 15. Nektar Therapeutics, San Francisco, CA, USA. 16. Consultant, Sebastopol, CA, USA. 17. University of California, San Francisco, CA, USA.
Abstract
BACKGROUND: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. PATIENTS AND METHODS: 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 LifeQuestionnaire (QLQ-BR23), was evaluated post randomisation in 733 of 852 patients with eitheranthracycline-, taxane- and capecitabine-pretreated locally recurrent or MBC randomised to etirinotecan pegol (n = 378; 145 mg/m2 every 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. RESULTS: 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. CONCLUSION: 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. STUDY NUMBER: NCT01492101.
RCT Entities:
BACKGROUND: 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. PATIENTS AND METHODS: 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/m2 every 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. RESULTS: 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. CONCLUSION: 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. STUDY NUMBER: NCT01492101.
Authors: Debu Tripathy; Sara M Tolaney; Andrew D Seidman; Carey K Anders; Nuhad Ibrahim; Hope S Rugo; Chris Twelves; Veronique Dieras; Volkmar Müller; Mary Tagliaferri; Alison L Hannah; Javier Cortés Journal: Future Oncol Date: 2019-05-10 Impact factor: 3.404
Authors: Leila Abou Salha; Flávia Costa Reis; Roberta Moreira Gonçalves; Jordão Horácio da Silva Lima; Nádia Abou Salha; Roney Pereira Pinto; José Elmo de Menezes; Eduardo Perez Oliveira; Pedro Lopes Ferreira; Maria Alves Barbosa Journal: Int J Equity Health Date: 2022-08-17