Association of KRAS and EGFR mutations with survival in patients with advanced lung adenocarcinomas
Open accessAbstract
BACKGROUND: Lung adenocarcinomas can be distinguished by identifying mutated driver oncogenes, including epidermal growth factor receptor (EGFR) and KRAS. Mutations in EGFR are associated with both improved survival as well as response to treatment with erlotinib and gefitinib. However, the prognostic significance of KRAS has not been evaluated in large numbers of patients and remains controversial. For the current report, the authors examined the association of EGFR and KRAS mutations with survival among patients with advanced lung adenocarcinomas. METHODS: Data were analyzed from patients with advanced lung adenocarcinomas who had known EGFR and KRAS mutation status evaluated between 2002 and 2009. The collected clinical variables included age, sex, Karnofsky performance status, smoking history, and treatment history. Overall survival from the diagnosis of advanced disease was analyzed using Kaplan-Meier and Cox proportional hazard methods. RESULTS: In total, 1036 patients were evaluated, including 610 women (59%) and 344 never-smokers (33%). The median patient age was 65 years (range, 25-92 years), and the majority of patients (81%) had a Karnofsky performance status ≥80%. In multivariate analysis, EGFR mutations were associated with longer overall survival (hazard ratio, 0.6; P < .001), and KRAS mutations were associated with shorter survival (hazard ratio, 1.21; P = .048). CONCLUSIONS: KRAS mutations predicted shorter survival for patients with advanced lung adenocarcinomas. The presence of EGFR and KRAS mutations define distinct subsets of patients with lung adenocarcinomas and should be determined in patients when they are diagnosed with advanced disease. Clinical trial reports should include EGFR and KRAS mutation status along with other prognostic factors.
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No co-expression of EGFR and KRAS mutations was found in any plasma samples.
“Consistent with prior reports, we found no co-expression of EGFR and KRAS mutations in any plasma samples (23, 39).”
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- Authors
- Johnson, M. L., Sima, C. S., Chaft, J., Paik, P. K., Pao, W., Kris, M. G., Ladanyi, M., & Riely, G. J.
- Affiliations
- Northwestern University (US)
- Memorial Sloan Kettering Cancer Center (US)
- Vanderbilt University (US)
- Corresponding author
- Johnson, Melissa L.
- ORCID
- Venue
- Cancer
- Publisher
- Wiley
- Published
- 2012-07-18
- Volume
- 119
- Issue
- 2
- Pages
- 356-362
- ISSN
- 0008-543X (ISSN-L)
- 1097-0142
- PMC
- PMC3966555
- OpenAlex
- W1599750485
- Cited by
- 166
- References
- 23
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 8 · 2023: 7 · 2022: 4 · 2021: 14 · 2020: 17 · 2019: 10 · 2018: 6 · 2017: 9 · 2016: 18 · 2015: 17 · 2014: 19 · 2013: 17 · 2012: 4
- FWCI
- 14.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (P30CA008748, T32CA009207, R25CA020449)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- lung adenocarcinoma, KRAS mutation, EGFR mutation, overall survival, prognostic factors, advanced lung cancer, cancer driver genes, molecular subtyping
- MeSH terms
- Adenocarcinoma of Lung, Adenocarcinoma, Adult, Aged, Aged, 80 and over, DNA Mutational Analysis, Female, Humans, Lung Neoplasms, Male, Middle Aged, Proto-Oncogene Proteins, Multivariate Analysis, Proportional Hazards Models, Proto-Oncogene Proteins p21(ras), ras Proteins, Kaplan-Meier Estimate, Genetic Association Studies, ErbB Receptors
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