Frequency and outcomes of brain metastases in patients with HER2-mutant lung cancers Journal Article


Authors: Offin, M.; Feldman, D.; Ni, A.; Myers, M. L.; Lai, W. V.; Pentsova, E.; Boire, A.; Daras, M.; Jordan, E. J.; Solit, D. B.; Arcila, M. E.; Jones, D. R.; Isbell, J. M.; Beal, K.; Young, R. J.; Rudin, C. M.; Riely, G. J.; Drilon, A.; Tabar, V.; DeAngelis, L. M.; Yu, H. A.; Kris, M. G.; Li, B. T.
Article Title: Frequency and outcomes of brain metastases in patients with HER2-mutant lung cancers
Abstract: Background: Mutations in human epidermal growth factor receptor 2 (HER2; also known as ERBB2) are found in approximately 2% of lung adenocarcinomas. The frequency and clinical course of brain metastases in this oncogenic subset are ill defined. Methods: Baseline and subsequent development of brain metastases was evaluated in consecutive patients with HER2-mutant (n = 98), epidermal growth factor receptor (EGFR)–mutant (n = 200), and KRAS-mutant lung cancers (n = 200). Results: At metastatic diagnosis, the odds ratio (ORs) for brain metastases was similar for patients whose tumors harbored HER2 mutations (19%) in comparison with patients with KRAS mutations (24%; OR for HER2 vs KRAS, 0.7; P =.33) but lower compared to patients with EGFR mutations (31%; OR for HER2 vs EGFR, 0.5; P =.03). Patients with lung cancer and HER2 mutations developed more brain metastases on treatment than patients with KRAS mutations (28% vs 8%; hazard ratio [HR], 5.2; P <.001) and trended more than patients with EGFR mutations (28% vs 16%; HR, 1.7; P =.06). Patients with HER2 YVMA mutations also developed more brain metastases on treatment than patients with KRAS mutations (HR, 5.9; P <.001). The median overall survival (OS) was shorter for patients with HER2-mutant (1.6 years; P <.001) or KRAS-mutant lung cancers (1.1 years; P <.001) than patients with EGFR-mutant lung cancers (3.0 years). Brain metastases occurred in 47% of patients with HER2-mutant lung cancers, which imparted shorter OS (HR, 2.7; P <.001). Conclusions: These data provide a framework for brain imaging surveillance in patients with HER2-mutant lung cancers and underpin the need to develop HER2-targeted agents with central nervous system activity. © 2019 American Cancer Society
Keywords: adult; aged; gene mutation; major clinical study; overall survival; mutation; disease course; cancer growth; comparative study; neuroimaging; lung neoplasms; morbidity; epidermal growth factor receptor; epidermal growth factor receptor 2; cohort analysis; lung cancer; oncogenes; brain metastasis; cancer epidemiology; receptor; egfr gene; k ras protein; electroencephalogram; erbb-2; molecularly targeted therapy; clinical outcome; kras gene; her2 gene; human; male; female; priority journal; article
Journal Title: Cancer
Volume: 125
Issue: 24
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2019-12-15
Start Page: 4380
End Page: 4387
Language: English
DOI: 10.1002/cncr.32461
PUBMED: 31469421
PROVIDER: scopus
PMCID: PMC6891113
DOI/URL:
Notes: Source: Scopus
Altmetric
Citation Impact
MSK Authors
  1. Robert J Young
    129 Young
  2. David Solit
    520 Solit
  3. Viviane S Tabar
    133 Tabar
  4. Helena Alexandra Yu
    127 Yu
  5. Kathryn Beal
    168 Beal
  6. Gregory J Riely
    406 Riely
  7. Maria Eugenia Arcila
    430 Arcila
  8. Mark Kris
    701 Kris
  9. Alexander Edward Drilon
    224 Drilon
  10. Adrienne Boire
    26 Boire
  11. Mariza Daras
    25 Daras
  12. Charles Rudin
    213 Rudin
  13. David Randolph Jones
    186 Jones
  14. Bob Tingkan Li
    95 Li
  15. Ai   Ni
    77 Ni
  16. James Michael Isbell
    43 Isbell
  17. Wei-Chu Victoria Lai
    16 Lai
  18. Michael David Offin
    39 Offin
  19. Mackenzie Myers
    9 Myers