Fiala Ondrej, Pesek Milos, Finek Jindrich, Benesova Lucie, Belsanova Barbora, Minarik Marek
Department of Oncology and Radiotherapy, Medical School and Teaching Hospital Pilsen, Charles University Prague, Czech Republic.
Cancer Genet. 2013 Jan-Feb;206(1-2):26-31. doi: 10.1016/j.cancergen.2012.12.003. Epub 2013 Jan 10.
The role of KRAS mutations in molecular targeted therapy by epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) has not been fully understood. The present investigation is aimed at an elucidation of the role of specific KRAS mutation types in predicting outcomes of patients with advanced NSCLC receiving EGFR-TKI therapy. Initially, 448 NSCLC patients were tested for the presence of KRAS mutations, to obtain frequencies of specific KRAS mutation types. Subsequently, the clinical outcome of treatment was evaluated in a subgroup of 38 KRAS-positive patients receiving EGFR-TKI therapy. KRAS mutations were detected in 69 of 448 patients (15.4%), mostly in smokers (17.86% vs. 5.8%, P = 0.0048), and appeared more frequently in adenocarcinomas than in squamous cell NSCLC or NSCLC that is not otherwise specified (21% vs. 6.99% vs. 4.4%, P = 0.0004). The most frequent type of KRAS mutation was G12C. The progression-free survival (PFS) was doubled in a group of non-G12C patients compared with that of the G12C group (9.0 wk vs. 4.3 wk, P = 0.009). The overall survival (OS) was not significantly different between non-G12C and G12C groups (12.1 wk vs. 9.3 wk, P = 0.068). The G12C KRAS mutation is a strong negative predictor for EGFR-TKI treatment, whereas other KRAS mutation types have not negatively predicted treatment efficacy compared with that for the wild-type KRAS genotype.
KRAS突变在非小细胞肺癌（NSCLC）表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）分子靶向治疗中的作用尚未完全明确。本研究旨在阐明特定KRAS突变类型在预测晚期NSCLC患者接受EGFR-TKI治疗结局中的作用。首先，对448例NSCLC患者进行KRAS突变检测，以获得特定KRAS突变类型的频率。随后，对38例接受EGFR-TKI治疗的KRAS阳性患者亚组的治疗临床结局进行评估。448例患者中有69例检测到KRAS突变（15.4%），大多为吸烟者（17.86%对5.8%，P = 0.0048），在腺癌中出现的频率高于鳞状细胞NSCLC或其他未明确类型的NSCLC（21%对6.99%对4.4%，P = 0.0004）。最常见的KRAS突变类型是G12C。非G12C组患者的无进展生存期（PFS）是G12C组的两倍（9.0周对4.3周，P = 0.009）。非G12C组和G12C组的总生存期（OS）无显著差异（12.1周对9.3周，P = 0.068）。G12C KRAS突变是EGFR-TKI治疗的强阴性预测指标，而与野生型KRAS基因型相比，其他KRAS突变类型未对治疗疗效产生负面预测。
