dc.contributor.author | Smyth, LM | |
dc.contributor.author | Batist, G | |
dc.contributor.author | Meric-Bernstam, F | |
dc.contributor.author | Kabos, P | |
dc.contributor.author | Spanggaard, I | |
dc.contributor.author | Lluch, A | |
dc.contributor.author | Jhaveri, K | |
dc.contributor.author | Varga, A | |
dc.contributor.author | Wong, A | |
dc.contributor.author | Schram, AM | |
dc.contributor.author | Ambrose, H | |
dc.contributor.author | Carr, TH | |
dc.contributor.author | de Bruin, EC | |
dc.contributor.author | Salinas-Souza, C | |
dc.contributor.author | Foxley, A | |
dc.contributor.author | Hauser, J | |
dc.contributor.author | Lindemann, JPO | |
dc.contributor.author | Maudsley, R | |
dc.contributor.author | McEwen, R | |
dc.contributor.author | Moschetta, M | |
dc.contributor.author | Nikolaou, M | |
dc.contributor.author | Schiavon, G | |
dc.contributor.author | Razavi, P | |
dc.contributor.author | Banerji, U | |
dc.contributor.author | Baselga, J | |
dc.contributor.author | Hyman, DM | |
dc.contributor.author | Chandarlapaty, S | |
dc.date.accessioned | 2021-05-14T08:17:05Z | |
dc.date.available | 2021-05-14T08:17:05Z | |
dc.date.issued | 2021-04-16 | |
dc.identifier.citation | NPJ breast cancer, 2021, 7 (1), pp. 44 - ? | |
dc.identifier.issn | 2374-4677 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4553 | |
dc.identifier.eissn | 2374-4677 | |
dc.identifier.doi | 10.1038/s41523-021-00251-7 | |
dc.description.abstract | Five to ten percent of ER+ metastatic breast cancer (MBC) tumors harbor somatic PTEN mutations. Loss of function of this tumor-suppressor gene defines a highly aggressive, treatment-refractory disease for which new therapies are urgently needed. This Phase I multipart expansion study assessed oral capivasertib with fulvestrant in patients with PTEN-mutant ER+ MBC. Safety and tolerability were assessed by standard methods. Plasma and tumor were collected for NGS and immunohistochemistry analyses of PTEN protein expression. In 31 eligible patients (12 fulvestrant naive; 19 fulvestrant pretreated), the 24-week clinical benefit rate was 17% in fulvestrant-naive and 42% in fulvestrant-pretreated patients, with objective response rate of 8% and 21%, respectively. Non-functional PTEN was centrally confirmed in all cases by NGS or immunohistochemistry. Co-mutations occurred in PIK3CA (32%), with less ESR1 (10% vs 72%) and more TP53 (40% vs 28%) alterations in fulvestrant-naive versus fulvestrant-pretreated patients, respectively. PTEN was clonally dominant in most patients. Treatment-related grade ≥3 adverse events occurred in 32% of patients, most frequently diarrhea and maculopapular rash (both n = 2). In this clinical study, which selectively targeted the aggressive PTEN-mutant ER+ MBC, capivasertib plus fulvestrant was tolerable and clinically active. Phenotypic and genomic differences were apparent between fulvestrant-naive and -pretreated patients.Trial registration number for the study is NCT01226316. | |
dc.format | Electronic | |
dc.format.extent | 44 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PORTFOLIO | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | Selective AKT kinase inhibitor capivasertib in combination with fulvestrant in PTEN-mutant ER-positive metastatic breast cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-03-24 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1038/s41523-021-00251-7 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2021-04-16 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | NPJ breast cancer | |
pubs.issue | 1 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Pharmacology – Adaptive Therapy | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Pharmacology – Adaptive Therapy | |
pubs.publication-status | Published | |
pubs.volume | 7 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Clinical Pharmacology – Adaptive Therapy | |
icr.researchteam | Clinical Pharmacology – Adaptive Therapy | |
dc.contributor.icrauthor | Banerji, Udai | |