Show simple item record

dc.contributor.authorPascual, J
dc.contributor.authorLim, JSJ
dc.contributor.authorMacpherson, IR
dc.contributor.authorArmstrong, AC
dc.contributor.authorRing, A
dc.contributor.authorOkines, AFC
dc.contributor.authorCutts, RJ
dc.contributor.authorHerrera-Abreu, MT
dc.contributor.authorGarcia-Murillas, I
dc.contributor.authorPearson, A
dc.contributor.authorHrebien, S
dc.contributor.authorGevensleben, H
dc.contributor.authorProszek, PZ
dc.contributor.authorHubank, M
dc.contributor.authorHills, M
dc.contributor.authorKing, J
dc.contributor.authorParmar, M
dc.contributor.authorProut, T
dc.contributor.authorFinneran, L
dc.contributor.authorMalia, J
dc.contributor.authorSwales, KE
dc.contributor.authorRuddle, R
dc.contributor.authorRaynaud, FI
dc.contributor.authorTurner, A
dc.contributor.authorHall, E
dc.contributor.authorYap, TA
dc.contributor.authorLopez, JS
dc.contributor.authorTurner, NC
dc.date.accessioned2020-10-12T13:54:20Z
dc.date.issued2020-09-21
dc.identifier.citationCancer discovery, 2020
dc.identifier.issn2159-8274
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4141
dc.identifier.eissn2159-8290
dc.identifier.doi10.1158/2159-8290.cd-20-0553
dc.description.abstractCyclin-dependent kinase 4/6 (CDK4/6) and PI3K inhibitors synergize in PIK3CA -mutant ER-positive HER2-negative breast cancer models. We conducted a phase Ib trial investigating the safety and efficacy of doublet CDK4/6 inhibitor palbociclib plus selective PI3K inhibitor taselisib in advanced solid tumors, and triplet palbociclib plus taselisib plus fulvestrant in 25 patients with PIK3CA -mutant, ER-positive HER2-negative advanced breast cancer. The triplet therapy response rate in PIK3CA- mutant, ER-positive HER2-negative cancer was 37.5% [95% confidence interval (CI), 18.8-59.4]. Durable disease control was observed in PIK3CA -mutant ER-negative breast cancer and other solid tumors with doublet therapy. Both combinations were well tolerated at pharmacodynamically active doses. In the triplet group, high baseline cyclin E1 expression associated with shorter progression-free survival (PFS; HR = 4.2; 95% CI, 1.3-13.1; P = 0.02). Early circulating tumor DNA (ctDNA) dynamics demonstrated high on-treatment ctDNA association with shorter PFS (HR = 5.2; 95% CI, 1.4-19.4; P = 0.04). Longitudinal plasma ctDNA sequencing provided genomic evolution evidence during triplet therapy. SIGNIFICANCE: The triplet of palbociclib, taselisib, and fulvestrant has promising efficacy in patients with heavily pretreated PIK3CA -mutant ER-positive HER2-negative advanced breast cancer. A subset of patients with PIK3CA -mutant triple-negative breast cancer derived clinical benefit from palbociclib and taselisib doublet, suggesting a potential nonchemotherapy targeted approach for this population.
dc.formatPrint-Electronic
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleTriplet Therapy with Palbociclib, Taselisib, and Fulvestrant in <i>PIK3CA</i>-Mutant Breast Cancer and Doublet Palbociclib and Taselisib in Pathway-Mutant Solid Cancers.
dc.typeJournal Article
dcterms.dateAccepted2020-09-16
rioxxterms.versionofrecord10.1158/2159-8290.cd-20-0553
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2020-09-21
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCancer discovery
pubs.notesNot 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/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Clinical PD Biomarker Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicine (de Bono Prostate)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical PD Biomarker Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/ICR-CTSU Urology and Head and Neck Trials Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics/Translational Genomics (hon.)
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/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Clinical PD Biomarker Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicine (de Bono Prostate)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical PD Biomarker Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/ICR-CTSU Urology and Head and Neck Trials Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics/Translational Genomics (hon.)
pubs.publication-statusPublished
pubs.embargo.termsNot known
icr.researchteamMolecular Oncologyen_US
icr.researchteamMedicine (de Bono Prostate)en_US
icr.researchteamClinical PD Biomarker Groupen_US
icr.researchteamICR-CTSU Urology and Head and Neck Trials Teamen_US
icr.researchteamTranslational Genomicsen_US
dc.contributor.icrauthorSwales, Karenen
dc.contributor.icrauthorPearson, Alexen
dc.contributor.icrauthorHall, Emmaen
dc.contributor.icrauthorGarcia-Murillas, Isaacen
dc.contributor.icrauthorHubank, Michaelen
dc.contributor.icrauthorPascual, Javieren
dc.contributor.icrauthorTurner, Nicholasen
dc.contributor.icrauthorLopez, Juanitaen


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record

https://creativecommons.org/licenses/by/4.0
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0