Differences in the survival of patients with recurrent versus de novo metastatic KRAS-mutant and EGFR-mutant lung adenocarcinomas Journal Article


Authors: Yu, H. A.; Sima, C. S.; Hellmann, M. D.; Naidoo, J.; Busby, N.; Rodriguez, K.; Riely, G. J.; Kris, M. G.
Article Title: Differences in the survival of patients with recurrent versus de novo metastatic KRAS-mutant and EGFR-mutant lung adenocarcinomas
Abstract: BACKGROUND Prognostic variables are independently associated with survival and are fundamental to clinical trial design. In the current study, the authors evaluated the impact of stage of disease at the time of the initial diagnosis on overall survival (OS) in 2 independent, oncogene-defined cohorts. METHODS All patients with epidermal growth factor receptor (EGFR)-mutant and KRAS-mutant metastatic lung adenocarcinomas were identified through routine molecular testing from January 2005 through January 2011. Clinical characteristics were obtained. OS from the date of diagnosis of recurrent or de novo metastatic disease was estimated using the Kaplan-Meier method. RESULTS A total of 635 patients with KRAS-mutant and 496 patients with EGFR-mutant metastatic lung adenocarcinomas were identified. Among patients with KRAS-mutant lung adenocarcinomas, those with de novo metastatic disease were found to have a shorter median OS compared with those with recurrent metastatic disease (13 months vs 18 months; P = .003). In a multivariable analysis of patients with KRAS-mutant lung adenocarcinomas, de novo metastatic disease at the time of diagnosis (TNM stage IV vs stage I-III: hazard ratio, 1.5 [95% confidence interval, 1.2-1.8]; P<.001) was independently associated with shorter OS. In patients with EGFR-mutant lung adenocarcinomas, after controlling for age and Karnofsky performance status, de novo metastatic disease at the time of diagnosis (stage IV vs stage I-III: hazard ratio, 1.3 [95% confidence interval, 1.0-1.7]; P = .03) was found to be independently associated with shorter OS. CONCLUSIONS Among patients with KRAS-mutant lung adenocarcinomas, stage of disease at diagnosis was associated with OS from the time of diagnosis of recurrent/metastatic disease. In multivariable analyses, in both patients with EGFR-mutant and KRAS-mutant lung adenocarcinomas, advanced stage at the time of diagnosis was found to be independently associated with shorter survival. Stage at diagnosis is a prognostic variable that should be accounted for in prospective studies in patients with metastatic lung adenocarcinomas. Cancer 2015;121:2078-2082. © 2015 American Cancer Society.
Keywords: adult; cancer survival; controlled study; aged; gene mutation; major clinical study; overall survival; cancer recurrence; cancer staging; disease association; epidermal growth factor receptor; cohort analysis; genetic association; lung cancer; gene function; oncogene; lung adenocarcinoma; karnofsky performance status; gene identification; sex difference; metastasis potential; age distribution; kras; oncogene k ras; k ras protein; stage; prognostic variables; cancer prognosis; very elderly; human; male; female; priority journal; article; epidermal growth factor receptor (egfr); oncogene egfr
Journal Title: Cancer
Volume: 121
Issue: 12
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2015-06-15
Start Page: 2078
End Page: 2082
Language: English
DOI: 10.1002/cncr.29313
PROVIDER: scopus
PUBMED: 25781862
PMCID: PMC4783794
DOI/URL:
Notes: Export Date: 2 July 2015 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Camelia S Sima
    204 Sima
  2. Helena Alexandra Yu
    97 Yu
  3. Gregory J Riely
    362 Riely
  4. Mark Kris
    636 Kris
  5. Matthew David Hellmann
    188 Hellmann
  6. Natalie Rose Busby
    4 Busby
  7. Jarushka Naidoo
    31 Naidoo