Afatinib in patients with metastatic or recurrent HER2-mutant lung cancers: A retrospective international multicentre study Journal Article


Authors: Lai, W. V.; Lebas, L.; Barnes, T. A.; Milia, J.; Ni, A.; Gautschi, O.; Peters, S.; Ferrara, R.; Plodkowski, A. J.; Kavanagh, J.; Sabari, J. K.; Clarke, S. J.; Pavlakis, N.; Drilon, A.; Rudin, C. M.; Arcila, M. E.; Leighl, N. B.; Shepherd, F. A.; Kris, M. G.; Mazières, J.; Li, B. T.
Article Title: Afatinib in patients with metastatic or recurrent HER2-mutant lung cancers: A retrospective international multicentre study
Abstract: Introduction: HER2 mutations occur in 1–3% of lung adenocarcinomas. With increasing use of next-generation sequencing at diagnosis, more patients with HER2-mutant tumours present for treatment. Few data are available to describe the clinical course and outcomes of these patients when treated with afatinib, a pan-HER inhibitor. Methods: We identified patients with metastatic or recurrent HER2-mutant lung adenocarcinomas treated with afatinib among seven institutions across Europe, Australia, and North America between 2009 and 2017. We determined the partial response rate to afatinib, types of HER2 mutations, duration of response, time on treatment, and survival. Results: We collected information on 27 patients with stage IV or recurrent HER2-mutant lung adenocarcinomas treated with afatinib. Of 23 patients evaluable for response, three partial responses were noted (13%, 95% confidence interval [CI] 4–33%). In addition, 57% of patients (13/23) had stable disease, and 30% (7/23) had progressive disease. We documented partial responses in patients with HER2 exon 20 insertions, including two with YVMA insertion and one with VAG insertion. Two patients with partial responses were previously treated with trastuzumab and pertuzumab. Median duration of response to afatinib was 6 months (range 5–10); median time on treatment was 3 months (range 1–30) and median overall survival from the date of diagnosis of metastatic or recurrent disease was 23 months (95% CI 18–53 months). Conclusions: Afatinib is modestly active in patients with HER2-mutant lung adenocarcinomas, including responses after progression on prior HER2-targeted therapies. However, investigations into the biology of HER2-mutant lung adenocarcinomas and development of better HER2-directed therapies are warranted. © 2018 Elsevier Ltd
Keywords: afatinib; her2 mutation; metastatic lung cancer; multicentre study
Journal Title: European Journal of Cancer
Volume: 109
ISSN: 0959-8049
Publisher: Elsevier Inc.  
Date Published: 2019-03-01
Start Page: 28
End Page: 35
Language: English
DOI: 10.1016/j.ejca.2018.11.030
PROVIDER: scopus
PUBMED: 30685684
DOI/URL:
Notes: Article -- Export Date: 1 February 2019 -- Source: Scopus
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MSK Authors
  1. Maria Eugenia Arcila
    328 Arcila
  2. Mark Kris
    581 Kris
  3. Alexander Edward Drilon
    132 Drilon
  4. Charles Rudin
    154 Rudin
  5. Bob Tingkan Li
    57 Li
  6. Ai   Ni
    45 Ni
  7. Joshua K Sabari
    20 Sabari
  8. Wei-Chu Victoria Lai
    10 Lai