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dc.contributor.authorSchmid, Pen_US
dc.contributor.authorAbraham, Jen_US
dc.contributor.authorChan, Sen_US
dc.contributor.authorWheatley, Den_US
dc.contributor.authorBrunt, AMen_US
dc.contributor.authorNemsadze, Gen_US
dc.contributor.authorBaird, RDen_US
dc.contributor.authorPark, YHen_US
dc.contributor.authorHall, PSen_US
dc.contributor.authorPerren, Ten_US
dc.contributor.authorStein, RCen_US
dc.contributor.authorMangel, Len_US
dc.contributor.authorFerrero, J-Men_US
dc.contributor.authorPhillips, Men_US
dc.contributor.authorConibear, Jen_US
dc.contributor.authorCortes, Jen_US
dc.contributor.authorFoxley, Aen_US
dc.contributor.authorde Bruin, ECen_US
dc.contributor.authorMcEwen, Ren_US
dc.contributor.authorStetson, Den_US
dc.contributor.authorDougherty, Ben_US
dc.contributor.authorSarker, S-Jen_US
dc.contributor.authorPrendergast, Aen_US
dc.contributor.authorMcLaughlin-Callan, Men_US
dc.contributor.authorBurgess, Men_US
dc.contributor.authorLawrence, Cen_US
dc.contributor.authorCartwright, Hen_US
dc.contributor.authorMousa, Ken_US
dc.contributor.authorTurner, NCen_US
dc.date.accessioned2020-03-04T11:42:44Z
dc.date.issued2020-02en_US
dc.identifier.citationJournal of clinical oncology : official journal of the American Society of Clinical Oncology, 2020, 38 (5), pp. 423 - 433en_US
dc.identifier.issn0732-183Xen_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3528
dc.identifier.eissn1527-7755en_US
dc.identifier.doi10.1200/jco.19.00368en_US
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.en_US
dc.formatPrint-Electronicen_US
dc.format.extent423 - 433en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/under-embargo-all-rights-reserveden_US
dc.titleCapivasertib Plus Paclitaxel Versus Placebo Plus Paclitaxel As First-Line Therapy for Metastatic Triple-Negative Breast Cancer: The PAKT Trial.en_US
dc.typeJournal Article
rioxxterms.versionofrecord10.1200/jco.19.00368en_US
rioxxterms.licenseref.startdate2020-02en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfJournal of clinical oncology : official journal of the American Society of Clinical Oncologyen_US
pubs.issue5en_US
pubs.notes6 monthsen_US
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-statusPublisheden_US
pubs.volume38en_US
pubs.embargo.terms6 monthsen_US
icr.researchteamMolecular Oncologyen_US
dc.contributor.icrauthorTurner, Nicholasen_US


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