dc.contributor.author | O'Leary, B | |
dc.contributor.author | Cutts, RJ | |
dc.contributor.author | Huang, X | |
dc.contributor.author | Hrebien, S | |
dc.contributor.author | Liu, Y | |
dc.contributor.author | André, F | |
dc.contributor.author | Loibl, S | |
dc.contributor.author | Loi, S | |
dc.contributor.author | Garcia-Murillas, I | |
dc.contributor.author | Cristofanilli, M | |
dc.contributor.author | Bartlett, CH | |
dc.contributor.author | Turner, NC | |
dc.date.accessioned | 2020-07-03T11:19:56Z | |
dc.date.issued | 2021-03-01 | |
dc.identifier.citation | Journal of the National Cancer Institute, 2020 | |
dc.identifier.issn | 0027-8874 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3797 | |
dc.identifier.eissn | 1460-2105 | |
dc.identifier.doi | 10.1093/jnci/djaa087 | |
dc.description.abstract | BACKGROUND: There are no established molecular biomarkers for patients with breast cancer receiving combination endocrine and CDK4/6 inhibitor (CDK4/6i). We aimed to determine whether genomic markers in circulating tumor DNA (ctDNA) can identify patients at higher risk of early progression on fulvestrant therapy with or without palbociclib, a CDK4/6i. METHODS: PALOMA-3 was a phase III, multicenter, double-blind randomized controlled trial of palbociclib plus fulvestrant (n = 347) vs placebo plus fulvestrant (n = 174) in patients with endocrine-pretreated estrogen receptor-positive (ER+) breast cancer. Pretreatment plasma samples from 459 patients were analyzed for mutations in 17 genes, copy number in 14 genes, and circulating tumor fraction. Progression-free survival (PFS) was compared in patients with circulating tumor fraction above or below a prespecified cutoff of 10% and with or without a specific genomic alteration. All statistical tests were 2-sided. RESULTS: Patients with high ctDNA fraction had worse PFS on both palbociclib plus fulvestrant (hazard ratio [HR] = 1.62, 95% confidence interval [CI] = 1.17 to 2.24; P = .004) and placebo plus fulvestrant (HR = 1.77, 95% CI = 1.21 to 2.59; P = .004). In multivariable analysis, high-circulating tumor fraction was associated with worse PFS (HR = 1.20 per 10% increase in tumor fraction, 95% CI = 1.09 to 1.32; P < .001), as was TP53 mutation (HR = 1.84, 95% CI = 1.27 to 2.65; P = .001) and FGFR1 amplification (HR = 2.91, 95% CI = 1.61 to 5.25; P < .001). No interaction with treatment randomization was observed. CONCLUSIONS: Pretreatment ctDNA identified a group of high-risk patients with poor clinical outcome despite the addition of CDK4/6 inhibition. These patients might benefit from inclusion in future trials of escalating treatment, with therapies that may be active in these genomic contexts. | |
dc.format | Print-Electronic | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | OXFORD UNIV PRESS INC | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | Circulating Tumor DNA Markers for Early Progression on Fulvestrant With or Without Palbociclib in ER+ Advanced Breast Cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2020-06-09 | |
rioxxterms.versionofrecord | 10.1093/jnci/djaa087 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2020-06-17 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Journal of the National Cancer Institute | |
pubs.notes | No embargo | |
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/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology | |
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/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology | |
pubs.publication-status | Published | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Molecular Oncology | |
dc.contributor.icrauthor | O'Leary, Benjamin | |
dc.contributor.icrauthor | Cutts, Rosalind | |
dc.contributor.icrauthor | Garcia-Murillas, Isaac | |
dc.contributor.icrauthor | Turner, Nicholas | |