Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Thoracic Medical Oncology Peking University Cancer Hospital & Institute Beijing China.
Thorac Cancer. 2016 Jan;7(1):24-31. doi: 10.1111/1759-7714.12266. Epub 2015 Jun 11.
Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) is the second most common mutated gene following epidermal growth factor receptor (EGFR) mutation in Chinese lung adenocarcinoma (LADC) patients. Investigating the clinical characteristics and outcomes of patients with co-existing KRAS and EGFR mutations can provide significant information for suitable therapies.
We retrospectively investigated 2106 LADC patients who had undergone EGFR and KRAS mutation tests at the Peking University Cancer Hospital. Only advanced LADC patients who carried KRAS and/or EGFR mutations, received EGFR-tyrosine kinase inhibitors (TKIs) and/or chemotherapy, and had completed follow-up analysis were analyzed further. KRAS and EGFR mutations were tested by denaturing high-performance liquid chromatography.
A KRAS mutation was detected in 123 out of 2106 LADC patients (5.8%) and 38 (1.8%) had a concurrent EGFR mutation. Seventy-two of 123 patients were advanced cases, which were divided into two sub-groups according to EGFR mutation status: overlapping KRAS and EGFR mutations (n = 24) and KRAS mutation alone (n = 48). Clinical characteristics of the two subgroups were similar. A greater ratio of patients with double mutations received EGFR-TKIs compared to KRAS mutation alone (75% vs. 43.8%, P = 0.012), and obtained a better objective response rate (38.9% vs. 9.5%, P = 0.027) and longer progression-free survival (8.0 vs. 1.5 months, P = 0.028) following EGFR-TKIs therapy. However, these differences were not observed in patients treated with platinum-based chemotherapy.
Overlapping KRAS and EGFR mutations occurred in 1.8% of Chinese LADC patients studied. The co-presence of EGFR mutations could predict a clinical benefit from EGFR-TKIs treatment for patients with KRAS mutations.
在中国人肺腺癌（LADC）患者中，Kirsten 大鼠肉瘤 2 病毒致癌基因同源物（KRAS）是继表皮生长因子受体（EGFR）突变之后第二常见的突变基因。研究同时存在 KRAS 和 EGFR 突变的患者的临床特征和结局，可以为合适的治疗方法提供重要信息。
我们回顾性调查了在北京大学肿瘤医院进行 EGFR 和 KRAS 突变检测的 2106 例 LADC 患者。仅对携带 KRAS 和/或 EGFR 突变、接受 EGFR 酪氨酸激酶抑制剂（TKI）和/或化疗且完成随访分析的晚期 LADC 患者进行进一步分析。KRAS 和 EGFR 突变通过变性高效液相色谱法进行检测。
在 2106 例 LADC 患者中，有 123 例（5.8%）检测到 KRAS 突变，38 例（1.8%）同时存在 EGFR 突变。在这 123 例患者中，有 72 例为晚期病例，根据 EGFR 突变状态分为两个亚组：重叠 KRAS 和 EGFR 突变（n=24）和 KRAS 突变单独存在（n=48）。两个亚组的临床特征相似。双重突变患者接受 EGFR-TKI 治疗的比例明显高于 KRAS 突变单独存在的患者（75% vs. 43.8%，P=0.012），且客观缓解率（38.9% vs. 9.5%，P=0.027）和无进展生存期（8.0 个月 vs. 1.5 个月，P=0.028）更长。然而，在接受铂类化疗的患者中未观察到这些差异。
在本研究中，重叠的 KRAS 和 EGFR 突变发生在 1.8%的中国 LADC 患者中。EGFR 突变的共存可以预测 KRAS 突变患者接受 EGFR-TKI 治疗的临床获益。
