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dc.contributor.authorChien, A Jo
dc.contributor.authorTripathy, Debasish
dc.contributor.authorAlbain, Kathy S
dc.contributor.authorSymmans, W Fraser
dc.contributor.authorRugo, Hope S
dc.contributor.authorMelisko, Michelle E
dc.contributor.authorWallace, Anne M
dc.contributor.authorSchwab, Richard
dc.contributor.authorHelsten, Teresa
dc.contributor.authorForero-Torres, Andres
dc.contributor.authorStringer-Reasor, Erica
dc.contributor.authorEllis, Erin D
dc.contributor.authorKaplan, Henry G
dc.contributor.authorNanda, Rita
dc.contributor.authorJaskowiak, Nora
dc.contributor.authorMurthy, Rashmi
dc.contributor.authorGodellas, Constantine
dc.contributor.authorBoughey, Judy C
dc.contributor.authorElias, Anthony D
dc.contributor.authorHaley, Barbara B
dc.contributor.authorKemmer, Kathleen
dc.contributor.authorIsaacs, Claudine
dc.contributor.authorClark, Amy S
dc.contributor.authorLang, Julie E
dc.contributor.authorLu, Janice
dc.contributor.authorKorde, Larissa
dc.contributor.authorEdmiston, Kirsten K
dc.contributor.authorNorthfelt, Donald W
dc.contributor.authorViscusi, Rebecca K
dc.contributor.authorYee, Douglas
dc.contributor.authorPerlmutter, Jane
dc.contributor.authorHylton, Nola M
dc.contributor.authorVan't Veer, Laura J
dc.contributor.authorDeMichele, Angela
dc.contributor.authorWilson, Amy
dc.contributor.authorPeterson, Garry
dc.contributor.authorBuxton, Meredith B
dc.contributor.authorPaoloni, Melissa
dc.contributor.authorClennell, Julia
dc.contributor.authorBerry, Scott
dc.contributor.authorMatthews, Jeffrey B
dc.contributor.authorSteeg, Katherine
dc.contributor.authorSinghrao, Ruby
dc.contributor.authorHirst, Gillian L
dc.contributor.authorSanil, Ashish
dc.contributor.authorYau, Christina
dc.contributor.authorAsare, Smita M
dc.contributor.authorBerry, Donald A
dc.contributor.authorEsserman, Laura J
dc.date.accessioned2020-09-04T23:13:47Z
dc.date.available2020-09-04T23:13:47Z
dc.date.issued2019-02-07
dc.identifier.citationChien, A. J., Tripathy, D., Albain, K. S., Symmans, W. F., Rugo, H. S., Melisko, M. E., ... & Stringer-Reasor, E. (2020). MK-2206 and standard neoadjuvant chemotherapy improves response in patients with human epidermal growth factor receptor 2–positive and/or hormone receptor–negative breast cancers in the I-SPY 2 trial. Journal of Clinical Oncology, 38(10), 1059-1069.en_US
dc.identifier.issn0732-183X
dc.identifier.pmid32031889
dc.identifier.doi10.1200/JCO.19.01027
dc.identifier.urihttp://hdl.handle.net/10150/642558
dc.description.abstractPURPOSE The phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin is a key pathway of survival and therapeutic resistance in breast cancer. We evaluated the pan-Akt inhibitor MK-2206 in combination with standard therapy in patients with high-risk early-stage breast cancer. PATIENTS AND METHODS I-SPY 2 is a multicenter, phase II, open-label, adaptively randomized neoadjuvant platform trial that screens experimental therapies and efficiently identifies potential predictive biomarker signatures. Patients are categorized by human epidermal growth factor receptor 2 (HER2), hormone receptor (HR), and MammaPrint statuses in a 2 x 2 x 2 layout. Patients within each of these 8 biomarker subtypes are adaptively randomly assigned to one of several experimental therapies, including MK-2206, or control. Therapies are evaluated for 10 biomarker signatures, each of which is a combination of these subtypes. The primary end point is pathologic complete response (pCR). A therapy graduates with one or more of these signatures if and when it has an 85% Bayesian predictive probability of success in a hypothetical phase III trial, adjusting for biomarker covariates. Patients in the current report received standard taxane- and anthracycline-based neoadjuvant therapy without (control) or with oral MK-2206 135 mg/week. RESULTS MK-2206 graduated with 94 patients and 57 concurrently randomly assigned controls in 3 graduation signatures: HR-negative/HER2-positive, HR-negative, and HER2-positive. Respective Bayesian mean covariate-adjusted pCR rates and percentage probability that MK-2206 is superior to control were 0.48:0.29 (97%), 0.62:0.36 (99%), and 0.46:0.26 (94%). In exploratory analyses, MK-2206 evinced a numerical improvement in event-free survival in its graduating signatures. The most significant grade 3-4 toxicity was rash (14% maculopapular, 8.6% acneiform). CONCLUSION The Akt inhibitor MK-2206 combined with standard neoadjuvant therapy resulted in higher estimated pCR rates in HR-negative and HER2-positive breast cancer. Although MK-2206 is not being further developed at this time, this class of agents remains of clinical interest.en_US
dc.language.isoenen_US
dc.publisherAMER SOC CLINICAL ONCOLOGYen_US
dc.rightsCopyright © 2020 American Society of Clinical Oncology. All rights reserved.en_US
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en_US
dc.titleMK-2206 and Standard Neoadjuvant Chemotherapy Improves Response in Patients With Human Epidermal Growth Factor Receptor 2-Positive and/or Hormone Receptor-Negative Breast Cancers in the I-SPY 2 Trialen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizonaen_US
dc.identifier.journalJOURNAL OF CLINICAL ONCOLOGYen_US
dc.description.note12 month embargo; published online: 7 February 2019en_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
dc.source.journaltitleJournal of clinical oncology : official journal of the American Society of Clinical Oncology
dc.source.volume38
dc.source.issue10
dc.source.beginpage1059
dc.source.endpage1069
dc.source.countryUnited States
dc.source.countryUnited States


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