Show simple item record

dc.contributor.authorSchmid, P
dc.contributor.authorAbraham, J
dc.contributor.authorChan, S
dc.contributor.authorWheatley, D
dc.contributor.authorBrunt, AM
dc.contributor.authorNemsadze, G
dc.contributor.authorBaird, RD
dc.contributor.authorPark, YH
dc.contributor.authorHall, PS
dc.contributor.authorPerren, T
dc.contributor.authorStein, RC
dc.contributor.authorMangel, L
dc.contributor.authorFerrero, J-M
dc.contributor.authorPhillips, M
dc.contributor.authorConibear, J
dc.contributor.authorCortes, J
dc.contributor.authorFoxley, A
dc.contributor.authorde Bruin, EC
dc.contributor.authorMcEwen, R
dc.contributor.authorStetson, D
dc.contributor.authorDougherty, B
dc.contributor.authorSarker, S-J
dc.contributor.authorPrendergast, A
dc.contributor.authorMcLaughlin-Callan, M
dc.contributor.authorBurgess, M
dc.contributor.authorLawrence, C
dc.contributor.authorCartwright, H
dc.contributor.authorMousa, K
dc.contributor.authorTurner, NC
dc.date.accessioned2020-03-04T11:42:44Z
dc.date.issued2020-02
dc.identifier.citationJournal of clinical oncology : official journal of the American Society of Clinical Oncology, 2020, 38 (5), pp. 423 - 433
dc.identifier.issn0732-183X
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3528
dc.identifier.eissn1527-7755
dc.identifier.doi10.1200/jco.19.00368
dc.description.abstractPURPOSE:The phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway is frequently activated in triple-negative breast cancer (TNBC). The AKT inhibitor capivasertib has shown preclinical activity in TNBC models, and drug sensitivity has been associated with activation of PI3K or AKT and/or deletions of PTEN. The PAKT trial was designed to evaluate the safety and efficacy of adding capivasertib to paclitaxel as first-line therapy for TNBC. PATIENTS AND METHODS:This double-blind, placebo-controlled, randomized phase II trial recruited women with untreated metastatic TNBC. A total of 140 patients were randomly assigned (1:1) to paclitaxel 90 mg/m2 (days 1, 8, 15) with either capivasertib (400 mg twice daily) or placebo (days 2-5, 9-12, 16-19) every 28 days until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), PFS and OS in the subgroup with PIK3CA/AKT1/PTEN alterations, tumor response, and safety. RESULTS:Median PFS was 5.9 months with capivasertib plus paclitaxel and 4.2 months with placebo plus paclitaxel (hazard ratio [HR], 0.74; 95% CI, 0.50 to 1.08; 1-sided P = .06 [predefined significance level, 1-sided P = .10]). Median OS was 19.1 months with capivasertib plus paclitaxel and 12.6 months with placebo plus paclitaxel (HR, 0.61; 95% CI, 0.37 to 0.99; 2-sided P = .04). In patients with PIK3CA/AKT1/PTEN-altered tumors (n = 28), median PFS was 9.3 months with capivasertib plus paclitaxel and 3.7 months with placebo plus paclitaxel (HR, 0.30; 95% CI, 0.11 to 0.79; 2-sided P = .01). The most common grade ≥ 3 adverse events in those treated with capivasertib plus paclitaxel versus placebo plus paclitaxel, respectively, were diarrhea (13% v 1%), infection (4% v 1%), neutropenia (3% v 3%), rash (4% v 0%), and fatigue (4% v 0%). CONCLUSION:Addition of the AKT inhibitor capivasertib to first-line paclitaxel therapy for TNBC resulted in significantly longer PFS and OS. Benefits were more pronounced in patients with PIK3CA/AKT1/PTEN-altered tumors. Capivasertib warrants further investigation for treatment of TNBC.
dc.formatPrint-Electronic
dc.format.extent423 - 433
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.subjectHumans
dc.subjectPaclitaxel
dc.subjectPyrimidines
dc.subjectPyrroles
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectPlacebos
dc.subjectDouble-Blind Method
dc.subjectSignal Transduction
dc.subjectAdult
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectProto-Oncogene Proteins c-akt
dc.subjectPTEN Phosphohydrolase
dc.subjectClass I Phosphatidylinositol 3-Kinases
dc.subjectTriple Negative Breast Neoplasms
dc.subjectProgression-Free Survival
dc.titleCapivasertib Plus Paclitaxel Versus Placebo Plus Paclitaxel As First-Line Therapy for Metastatic Triple-Negative Breast Cancer: The PAKT Trial.
dc.typeJournal Article
rioxxterms.versionofrecord10.1200/jco.19.00368
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
rioxxterms.licenseref.startdate2020-02
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJournal of clinical oncology : official journal of the American Society of Clinical Oncology
pubs.issue5
pubs.notes6 months
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-statusPublished
pubs.volume38
pubs.embargo.terms6 months
icr.researchteamMolecular Oncologyen_US
dc.contributor.icrauthorTurner, Nicholasen


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record