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Region Hovedstaden - en del af Københavns Universitetshospital
E-pub ahead of print

Efficacy and Determinants of Response to HER Kinase Inhibition in HER2-Mutant Metastatic Breast Cancer

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. A large scale analysis of genetic variants within putative miRNA binding sites in prostate cancer

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Pharmacokinetics and Safety of Olaparib in Patients with Advanced Solid Tumours and Renal Impairment

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Lillian M Smyth
  • Sarina A Piha-Paul
  • Helen H Won
  • Alison M Schram
  • Cristina Saura
  • Sherene Loi
  • Janice Lu
  • Geoffrey I Shapiro
  • Dejan Juric
  • Ingrid A Mayer
  • Carlos L Arteaga
  • Macarena I de la Fuente
  • Adam M Brufksy
  • Iben Spanggaard
  • Morten Mau-Sorensen
  • Monica Arnedos
  • Victor Moreno
  • Valentina Boni
  • Joohyuk Sohn
  • Lee S Schwartzberg
  • Xavier Gonzalez-Farre
  • Andres Cervantes
  • Francois-Clement Bidard
  • Alexander N Gorelick
  • Richard B Lanman
  • Rebecca J Nagy
  • Gary A Ulaner
  • Sarat Chandarlapaty
  • Komal Jhaveri
  • Elena I Gavrila
  • Catherine Zimel
  • S Duygu Selcuklu
  • Myra Melcer
  • Aliaksandra Samoila
  • Yanyan Cai
  • Maurizio Scaltriti
  • Grace Mann
  • Feng Xu
  • Lisa D Eli
  • Melanie Dujka
  • Alshad S Lalani
  • Richard Bryce
  • Jose Baselga
  • Barry S Taylor
  • David B Solit
  • Funda Meric-Bernstam
  • David M Hyman
Vis graf over relationer

HER2 mutations define a subset of metastatic breast cancers with a unique mechanism of oncogenic addiction to HER2 signaling. We explored activity of the irreversible pan-HER kinase inhibitor neratinib, alone or with fulvestrant, in 81 patients with HER2-mutant metastatic breast cancer. Overall response rate was similar with or without estrogen receptor (ER) blockade. By comparison, progression-free survival and duration of response appeared longer in ER+ patients receiving combination therapy, although the study was not designed for direct comparison. Pre-existent concurrent activating HER2 or HER3 alterations were associated with poor treatment outcome. Similarly, acquisition of multiple HER2-activating events, as well as gatekeeper alterations, were observed at disease progression in a high proportion of patients deriving clinical benefit from neratinib. Collectively these data define HER2 mutations as a therapeutic target in breast cancer and suggest that co-existence of additional HER signaling alterations may promote both de novo and acquired resistance to neratinib.

OriginalsprogEngelsk
TidsskriftCancer Discovery
ISSN2159-8274
DOI
StatusE-pub ahead of print - 2020

Bibliografisk note

Copyright ©2019, American Association for Cancer Research.

ID: 58961138