Korean J Intern Med.  2017 May;32(3):514-522. 10.3904/kjim.2015.299.

KRAS G₁₂C mutation as a poor prognostic marker of pemetrexed treatment in non-small cell lung cancer

• Park S
• Kim JY
• Lee SH
• Suh B
• Keam B
• Kim TM
• Kim DW
• Heo DS

• KMID: 2379482
• DOI: http://doi.org/10.3904/kjim.2015.299

Abstract

BACKGROUND/AIMS
The predictive and prognostic value of KRAS mutation and its type of mutations in non-small cell lung cancer (NSCLC) are controversial. This clinical study was designed to investigate the predictive value of KRAS mutations and its mutation types to pemetrexed and gemcitabine based treatment.
METHODS
Advanced NSCLC patients tested for KRAS mutation (n = 334) were retrospectively reviewed and 252 patients with wild type epidermal growth factor receptor and no anaplastic lymphoma kinase fusion were enrolled for the analysis. KRAS mutations were observed in 45 subjects with mutation type as followed: G₁₂C (n = 13), G₁₂D (n = 12), G₁₂V (n = 12), other (n = 8). Response rate (RR), progression-free survival (PFS), and overall survival (OS) of pemetrexed singlet and gemcitabine based chemotherapy were analysis.
RESULTS
Age, sex, performance status were well balanced between subjects with or without KRAS mutations. No difference was observed in RR. Hazard ratio (HR) of PFS for pemetrexed treated subjects with G₁₂C mutation compared to subjects with KRAS wild type was 1.96 (95% confidential interval [CI], 1.01 to 3.79; p = 0.045), but other mutations failed to show clinical significance. By analysis done by PFS, compared to the subjects with transition mutation, HR was 1.48 (95% CI, 0.64 to 3.40; p = 0.360) for subjects with transversion mutation on pemetrexed treatment and 0.41 (95% CI, 0.19 to 0.87; p = 0.020) for subjects treated with gemcitabine based chemotherapy. No difference was observed in OS.
CONCLUSIONS
In this study, different drug sensitivity was observed according to the type of KRAS mutation. NSCLC subpopulations with different KRAS mutation type should be considered as different subgroups and optimal chemotherapy regimens should be searched in further confirmative studies.

Keyword

KRAS; Pemetrexed; Gemcitabine; Carcinoma, non-small-cell lung

MeSH Terms

Carcinoma, Non-Small-Cell Lung*
Clinical Study
Disease-Free Survival
Drug Therapy
Humans
Lymphoma
Pemetrexed*
Phosphotransferases
Receptor, Epidermal Growth Factor
Retrospective Studies
Pemetrexed
Phosphotransferases
Receptor, Epidermal Growth Factor