XENERA-1: a randomised double-blind Phase II trial of xentuzumab in combination with everolimus and exemestane versus everolimus and exemestane in patients with hormone receptor-positive/HER2-negative metastatic breast cancer and non-visceral disease

Breast Cancer Research

Research

Navid Baktash¹  Tsvetan Biyukov²  Julie Lemieux³  Peter Schmid⁴  Ana Joaquim⁵  Dan Massey⁶  Lowell Hart⁷  Serafín Morales⁸  José Ángel García-Sáenz⁹  Tamara Díaz-Redondo^1,10  Javier Cortes^1,11  Sibel Blau^1,12  Noelia Martínez Jañez^1,13  Howard A. Burris^1,14  Patrick Neven^1,15  Hope S. Rugo^1,16 

[1] Boehringer Ingelheim (Canada) Ltd, Burlington, ON, Canada;Boehringer Ingelheim International GmbH, Ingelheim, Germany;Centre Hospitalier Universitaire de Québec-Université Laval Research Centre, Quebec, Canada;Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London, UK;Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal;Elderbrook Solutions GmbH on behalf of Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany;Florida Cancer Specialists, Fort Myers, FL, USA;Hospital Arnau de Vilanova, Lleida, Spain;Hospital Clínico San Carlos, Madrid, Spain;Hospitales Universitarios Regional y Virgen de la Victoria de Málaga, Unidad de Gestión Clínica Intercentros de Oncología, Málaga, Spain;International Breast Cancer Center (IBCC), Pangaea Oncology, Quironsalud Group, Barcelona, Spain;Faculty of Biomedical and Health Sciences, Department of Medicine, Universidad Europea de Madrid, Madrid, Spain;Northwest Medical Specialties, Tacoma, WA, USA;Ramon y Cajal University Hospital, Madrid, Spain;Sarah Cannon Research Institute, Nashville, TN, USA;UZ Leuven, Leuven, Belgium;University of California at San Francisco, San Francisco, CA, USA;

关键词: Advanced breast cancer;    HR+/HER2−;    Non-visceral disease;    Xentuzumab;    Insulin-like growth factor;    Everolimus;    Exemestane;   

DOI  :  10.1186/s13058-023-01649-w

 received in 2023-01-04, accepted in 2023-04-20,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundXentuzumab is a humanised monoclonal antibody that binds to IGF-1 and IGF-2, neutralising their proliferative activity and restoring inhibition of AKT by everolimus. This study evaluated the addition of xentuzumab to everolimus and exemestane in patients with advanced breast cancer with non-visceral disease.MethodsThis double-blind, randomised, Phase II study was undertaken in female patients with hormone-receptor (HR)-positive/human epidermal growth factor 2 (HER2)-negative advanced breast cancer with non-visceral disease who had received prior endocrine therapy with or without CDK4/6 inhibitors. Patients received a weekly intravenous infusion of xentuzumab (1000 mg) or placebo in combination with everolimus (10 mg/day orally) and exemestane (25 mg/day orally). The primary endpoint was progression-free survival (PFS) per independent review.ResultsA total of 103 patients were randomised and 101 were treated (n = 50 in the xentuzumab arm and n = 51 in the placebo arm). The trial was unblinded early due to high rates of discordance between independent and investigator assessment of PFS. Per independent assessment, median PFS was 12.7 (95% CI 6.8–29.3) months with xentuzumab and 11.0 (7.7–19.5) months with placebo (hazard ratio 1.19; 95% CI 0.55–2.59; p = 0.6534). Per investigator assessment, median PFS was 7.4 (6.8–9.7) months with xentuzumab and 9.2 (5.6–14.4) months with placebo (hazard ratio 1.23; 95% CI 0.69–2.20; p = 0.4800). Tolerability was similar between the arms, with diarrhoea (33.3–56.0%), fatigue (33.3–44.0%) and headache (21.6–40.0%) being the most common treatment-emergent adverse events. The incidence of grade ≥ 3 hyperglycaemia was similar between the xentuzumab (2.0%) and placebo (5.9%) arms.ConclusionsWhile this study demonstrated that xentuzumab could be safely combined with everolimus and exemestane in patients with HR-positive/HER2-negative advanced breast cancer with non-visceral disease, there was no PFS benefit with the addition of xentuzumab.Trial registration ClinicalTrials.gov, NCT03659136. Prospectively registered, September 6, 2018.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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