Distinct clinical course of EGFR-mutant resected lung cancers: Results of testing of 1118 surgical specimens and effects of adjuvant gefitinib and erlotinib Journal Article


Authors: D'Angelo, S. P.; Janjigian, Y. Y.; Ahye, N.; Riely, G. J.; Chaft, J. E.; Sima, C. S.; Shen, R.; Zheng, J.; Dycoco, J.; Kris, M. G.; Zakowski, M. F.; Ladanyi, M.; Rusch, V.; Azzoli, C. G.
Article Title: Distinct clinical course of EGFR-mutant resected lung cancers: Results of testing of 1118 surgical specimens and effects of adjuvant gefitinib and erlotinib
Abstract: BACKGROUND:: EGFR and KRAS mutations are mutually exclusive and predict outcomes with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment in patients with stage IV lung cancers. The clinical significance of these mutations in patients with resected stage I-III lung cancers is unclear. METHODS:: At our institution, resection specimens from patients with stage I-III lung adenocarcinomas are tested for the presence of EGFR or KRAS mutations during routine pathology analysis such that the results are available before consideration of adjuvant therapy. In a cohort of 1118 patients tested over 8 years, overall survival was analyzed using multivariate analysis to control for potential confounders, including age, sex, stage, and smoking history. The impact of adjuvant erlotinib or gefitinib was examined in an independent data set of patients exclusively with EGFR mutation, in which date of recurrence was recorded. RESULTS:: In the overall population, we identified 227 KRAS (25%) and 222 EGFR (20%) mutations. Patients with EGFR-mutant lung cancers had a lower risk of death compared with those without EGFR mutations, overall survival (OS) HR 0.51 (95% confidence interval [CI]: 0.34-0.76, p < 0.001). Patients with KRAS-mutant lung cancers had similar outcomes compared with individuals with KRAS wild-type tumors, OS HR 1.17 (95% CI: 0.87-1.57, p = 0.30). A separate data set includes only patients with EGFR-mutant lung cancers identified over 10 years (n = 286). In patients with resected lung cancers and EGFR mutation, treatment with adjuvant erlotinib or gefitinib was associated with a lower risk of recurrence or death, disease-free survival HR 0.43 (95% CI: 0.26-0.72, p = 0.001), and a trend toward improved OS. CONCLUSIONS:: Patients with resected stage I-III lung cancers and EGFR mutation have a lower risk of death compared with patients without EGFR mutation. This may be because of treatment with EGFR TKIs. Patients with, and without KRAS mutation have similar OS. These data support reflex testing of resected lung adenocarcinomas for EGFR mutation to provide prognostic information and identify patients for enrollment on prospective clinical trials of adjuvant EGFR TKIs. © 2012 by the International Association for the Study of Lung Cancer.
Keywords: adult; cancer chemotherapy; aged; cancer surgery; major clinical study; overall survival; mutation; disease course; mortality; cancer recurrence; cisplatin; erlotinib; cancer radiotherapy; disease free survival; outcome assessment; disease association; epidermal growth factor receptor; wild type; risk factor; cause of death; disease severity; lung adenocarcinoma; gefitinib; egfr; kras; k ras protein; early-stage; adenocarcinomas; lung cancers; non-small cell lung cancers; resected
Journal Title: Journal of Thoracic Oncology
Volume: 7
Issue: 12
ISSN: 1556-0864
Publisher: Elsevier Inc.  
Date Published: 2012-12-01
Start Page: 1815
End Page: 1822
Language: English
DOI: 10.1097/JTO.0b013e31826bb7b2
PROVIDER: scopus
PUBMED: 23154553
DOI/URL:
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 2 January 2013" - "Source: Scopus"
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MSK Authors
  1. Camelia S Sima
    204 Sima
  2. Junting Zheng
    133 Zheng
  3. Valerie W Rusch
    657 Rusch
  4. Christopher G Azzoli
    105 Azzoli
  5. Ronglai Shen
    129 Shen
  6. Yelena Yuriy Janjigian
    148 Janjigian
  7. Marc Ladanyi
    879 Ladanyi
  8. Jamie Erin Chaft
    127 Chaft
  9. Gregory J Riely
    350 Riely
  10. Maureen F Zakowski
    280 Zakowski
  11. Joseph Dycoco
    22 Dycoco
  12. Mark Kris
    612 Kris
  13. Nicholas Michael Ahye
    1 Ahye