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.

Autor: Schmid P; Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London, UK. p.schmid@qmul.ac.uk., Cortes J; 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., Joaquim A; Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal., Jañez NM; Ramon y Cajal University Hospital, Madrid, Spain., Morales S; Hospital Arnau de Vilanova, Lleida, Spain., Díaz-Redondo T; Hospitales Universitarios Regional y Virgen de la Victoria de Málaga, Unidad de Gestión Clínica Intercentros de Oncología, Málaga, Spain., Blau S; Northwest Medical Specialties, Tacoma, WA, USA., Neven P; UZ Leuven, Leuven, Belgium., Lemieux J; Centre Hospitalier Universitaire de Québec-Université Laval Research Centre, Quebec, Canada., García-Sáenz JÁ; Hospital Clínico San Carlos, Madrid, Spain., Hart L; Florida Cancer Specialists, Fort Myers, FL, USA., Biyukov T; Boehringer Ingelheim International GmbH, Ingelheim, Germany., Baktash N; Boehringer Ingelheim (Canada) Ltd, Burlington, ON, Canada., Massey D; Elderbrook Solutions GmbH on behalf of Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany., Burris HA 3rd; Sarah Cannon Research Institute, Nashville, TN, USA., Rugo HS; University of California at San Francisco, San Francisco, CA, USA.
Jazyk: angličtina
Zdroj: Breast cancer research : BCR [Breast Cancer Res] 2023 Jun 12; Vol. 25 (1), pp. 67. Date of Electronic Publication: 2023 Jun 12.
DOI: 10.1186/s13058-023-01649-w
Abstrakt: Background: Xentuzumab 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.
Methods: This 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.
Results: A 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.
Conclusions: While 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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