Management of brain metastases in tyrosine kinase inhibitor-naïve epidermal growth factor receptor-mutant non-small-cell lung cancer: A retrospective multi-institutional analysis Journal Article


Authors: Magnuson, W. J.; Lester-Coll, N. H.; Wu, A. J.; Yang, T. J.; Lockney, N. A.; Gerber, N. K.; Beal, K.; Amini, A.; Patil, T.; Kavanagh, B. D.; Camidge, D. R.; Braunstein, S. E.; Boreta, L. C.; Balasubramanian, S. K.; Ahluwalia, M. S.; Rana, N. G.; Attia, A.; Gettinger, S. N.; Contessa, J. N.; Yu, J. B.; Chiang, V. L.
Article Title: Management of brain metastases in tyrosine kinase inhibitor-naïve epidermal growth factor receptor-mutant non-small-cell lung cancer: A retrospective multi-institutional analysis
Abstract: Purpose Stereotactic radiosurgery (SRS), whole-brain radiotherapy (WBRT), and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are treatment options for brain metastases in patients with EGFR-mutant non-small-cell lung cancer (NSCLC). This multi-institutional analysis sought to determine the optimal management of patients with EGFR-mutant NSCLC who develop brain metastases and have not received EGFR-TKI. Materials and Methods A total of 351 patients from six institutions with EGFR-mutant NSCLC developed brain metastases and met inclusion criteria for the study. Exclusion criteria included prior EGFR-TKI use, EGFR-TKI resistance mutation, failure to receive EGFR-TKI after WBRT/SRS, or insufficient follow-up. Patients were treated with SRS followed by EGFR-TKI, WBRT followed by EGFR-TKI, or EGFR-TKI followed by SRS or WBRT at intracranial progression. Overall survival (OS) and intracranial progression-free survival were measured from the date of brain metastases. Results ThemedianOS for the SRS (n = 100),WBRT (n = 120), and EGFR-TKI (n = 131) cohortswas 46, 30, and 25 months, respectively (P, .001). On multivariable analysis, SRS versus EGFR-TKI, WBRT versus EGFR-TKI, age, performance status, EGFR exon 19mutation, and absence of extracranialmetastases were associatedwith improved OS. Although the SRS and EGFR-TKI cohorts shared similar prognostic features, the WBRT cohort was more likely to have a less favorable prognosis (P = .001). Conclusion This multi-institutional analysis demonstrated that the use of upfront EGFR-TKI, and deferral of radiotherapy, is associated with inferior OS in patients with EGFR-mutant NSCLC who develop brain metastases. SRS followed by EGFR-TKI resulted in the longest OS and allowed patients to avoid the potential neurocognitive sequelae ofWBRT. A prospective, multi-institutional randomized trial of SRS followed by EGFR-TKI versus EGFR-TKI followed by SRS at intracranial progression is urgently needed. © 2017 by American Society of Clinical Oncology.
Journal Title: Journal of Clinical Oncology
Volume: 35
Issue: 10
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2017-04-01
Start Page: 1070
End Page: 1077
Language: English
DOI: 10.1200/jco.2016.69.7144
PROVIDER: scopus
PUBMED: 28113019
DOI/URL:
Notes: Article -- Export Date: 2 May 2017 -- Source: Scopus
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MSK Authors
  1. Kathryn Beal
    157 Beal
  2. Naamit Kurshan Gerber
    18 Gerber
  3. Abraham Jing-Ching Wu
    199 Wu
  4. T. Jonathan Yang
    64 Yang
  5. Natalie Ausborn Lockney
    29 Lockney