Show simple item record

 
dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorSchmid, Peter
dc.contributor.authorSablin, Marie-Paule
dc.contributor.authorBergh, Jonas
dc.contributor.authorIm, Seock-Ah
dc.contributor.authorLu, Yen-Shen
dc.contributor.authorMartínez, Noelia
dc.contributor.authorCortés Castan, Javier
dc.date.accessioned2021-06-29T10:09:04Z
dc.date.available2021-06-29T10:09:04Z
dc.date.issued2021-01-15
dc.identifier.citationSchmid P, Sablin MP, Bergh J, Im SA, Lu YS, Martínez N, et al. A phase Ib/II study of xentuzumab, an IGF-neutralising antibody, combined with exemestane and everolimus in hormone receptor-positive, HER2-negative locally advanced/metastatic breast cancer. Breast Cancer Res. 2021 Jan 15;23:8.
dc.identifier.issn1465-542X
dc.identifier.urihttp://hdl.handle.net/11351/6097
dc.descriptionBreast cancer; HER2-negative; Hormone receptor-positive
dc.description.abstractBackground Xentuzumab—a humanised IgG1 monoclonal antibody—binds IGF-1 and IGF-2, inhibiting their growth-promoting signalling and suppressing AKT activation by everolimus. This phase Ib/II exploratory trial evaluated xentuzumab plus everolimus and exemestane in hormone receptor-positive, locally advanced and/or metastatic breast cancer (LA/MBC). Methods Patients with hormone receptor-positive/HER2-negative LA/MBC resistant to non-steroidal aromatase inhibitors were enrolled. Maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of xentuzumab/everolimus/exemestane were determined in phase I (single-arm, dose-escalation). In phase II (open-label), patients were randomised 1:1 to the RP2D of xentuzumab/everolimus/exemestane or everolimus/exemestane alone. Randomisation was stratified by the presence of visceral metastases. Primary endpoint was progression-free survival (PFS). Results MTD was determined as xentuzumab 1000 mg weekly plus everolimus 10 mg/day and exemestane 25 mg/day. A total of 140 patients were enrolled in phase II (70 to each arm). Further recruitment was stopped following an unfavourable benefit-risk assessment by the internal Data Monitoring Committee appointed by the sponsor. Xentuzumab was discontinued; patients could receive everolimus/exemestane if clinically indicated. Median PFS was 7.3 months (95% CI 3.3–not calculable) in the xentuzumab/everolimus/exemestane group and 5.6 months (3.7–9.1) in the everolimus/exemestane group (hazard ratio 0.97, 95% CI 0.57–1.65; P = 0.9057). In a pre-specified subgroup of patients without visceral metastases at screening, xentuzumab/everolimus/exemestane showed evidence of PFS benefit versus everolimus/exemestane (hazard ratio 0.21 [0.05–0.98]; P = 0.0293). Most common any-cause adverse events in phase II were diarrhoea (29 [41.4%] in the xentuzumab/everolimus/exemestane group versus 20 [29.0%] in the everolimus/exemestane group), mucosal inflammation (27 [38.6%] versus 21 [30.4%]), stomatitis (24 [34.3%] versus 24 [34.8%]), and asthenia (21 [30.0%] versus 24 [34.8%]). Conclusions Addition of xentuzumab to everolimus/exemestane did not improve PFS in the overall population, leading to early discontinuation of the trial. Evidence of PFS benefit was observed in patients without visceral metastases when treated with xentuzumab/everolimus/exemestane, leading to initiation of the phase II XENERA™-1 trial (NCT03659136).
dc.language.isoeng
dc.publisherBMC
dc.relation.ispartofseriesBreast Cancer Research;23
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectMedicaments - Eficàcia
dc.subjectMama - Càncer - Tractament
dc.subject.meshBreast Neoplasms
dc.subject.meshDrug Therapy, Combination
dc.subject.meshTreatment Outcome
dc.titleA phase Ib/II study of xentuzumab, an IGF-neutralising antibody, combined with exemestane and everolimus in hormone receptor-positive, HER2-negative locally advanced/metastatic breast cancer
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1186/s13058-020-01382-8
dc.subject.decsneoplasias de la mama
dc.subject.decsfarmacoterapia combinada
dc.subject.decsresultado del tratamiento
dc.relation.publishversionhttps://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-020-01382-8
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Schmid P] Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London, UK. [Sablin MP] Department of Drug Development and Innovation, Institut Curie, Paris, France. [Bergh J] Department of Oncology-Pathology, Karolinska Institutet and Breast Cancer Centre, Cancer Theme, Karolinska University Hospital, Stockholm, Sweden. [Im SA] Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. [Lu YS] Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan. [Martínez N] Department of Oncology, Ramon y Cajal University Hospital, Madrid, Spain. [Cortés J] Breast Cancer Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Department of Oncology, IOB Institute of Oncology, Quironsalud Group, Madrid and Barcelona, Spain
dc.identifier.pmid33451345
dc.identifier.wos000608053300001
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record