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J Thorac Oncol. 2019 Feb 5. pii: S1556-0864(19)30097-8. doi: 10.1016/j.jtho.2019.01.020. [Epub ahead of print]

Characteristics and outcomes of patients with metastatic KRAS mutant lung adenocarcinomas: The Lung Cancer Mutation Consortium experience.

Author information

1
Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA.
2
Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA.
3
Center for Quantitative Sciences, Vanderbilt University School of Medicine, Nashville, TN.
4
Department of Pathology and Laboratory Medicine, Winship Cancer Institute of Emory University, Atlanta, GA.
5
Department of Thoracic Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.
6
Lung Cancer Program, Dana-Farber Harvard Cancer Center, Boston, MA.
7
Department of Pathology, University of Colorado Denver School of Medicine, Aurora, CO.
8
Division of Medical Oncology, University of Colorado Denver School of Medicine, Aurora, CO.
9
Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA. Electronic address: ssramal@emory.edu.

Abstract

BACKGROUND:

Mutations in the KRAS gene are the most common driver oncogenes present in lung adenocarcinomas. We analyzed the largest multi-institutional database available containing patients with metastatic KRAS mutant lung adenocarcinomas.

METHODS:

The Lung Cancer Mutation Consortium (LCMC) is a multi-institutional collaboration to study the genomic characteristics of lung adenocarcinomas, treat them with genomically directed therapeutic approaches, and assess their outcomes. Since its inception in 2009, the LCMC has enrolled over 1900 patients and has performed pretreatment, multiplexed, molecular characterization along with collecting clinical data. We evaluated the characteristics of patients with KRAS mutation in the LCMC and the association with overall survival (OS).

RESULTS:

Data from 1655 patients with metastatic lung adenocarcinomas were analyzed. 450 (27%) patients had a KRAS mutation, 58% female, 93% smokers, and median age of 65 years. Main KRAS subtypes were: G12C 39%; G12D and G12V at 18% each. Among patients with KRAS mutation, G12D had a higher proportion of never smokers (22%, P<0.001). Patients with KRAS mutant tumors had a trend toward shorter median survival compared to all others in the series (1.96 vs. 2.22; P=0.08) and lower 2-year survival rate (49% (95% CI: 44-54%) and 55% (95% CI: 52-58%), respectively.

CONCLUSIONS:

In the LCMC study, 27% of lung adenocarcinomas patients harbored a KRAS mutation and up to third of them had another oncogenic driver. Patients with both KRAS and STK11 mutations had a significantly inferior clinical outcome.

PMID:
30735816
DOI:
10.1016/j.jtho.2019.01.020

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