KRAS G₁₂C mutation as a poor prognostic marker of pemetrexed treatment in non-small cell lung cancer.
- Author:
Sehhoon PARK
1
;
Ji Yeon KIM
;
Se Hoon LEE
;
Beomseok SUH
;
Bhumsuk KEAM
;
Tae Min KIM
;
Dong Wan KIM
;
Dae Seog HEO
Author Information
- Publication Type:Original Article
- Keywords: KRAS; Pemetrexed; Gemcitabine; Carcinoma, non-small-cell lung
- MeSH: Carcinoma, Non-Small-Cell Lung*; Clinical Study; Disease-Free Survival; Drug Therapy; Humans; Lymphoma; Pemetrexed*; Phosphotransferases; Receptor, Epidermal Growth Factor; Retrospective Studies
- From:The Korean Journal of Internal Medicine 2017;32(3):514-522
- CountryRepublic of Korea
- Language:English
- 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.
