title: Clinical outcome of epidermal growth factor receptor-tyrosine kinase inhibitors therapy for patients with overlapping kirsten rat sarcoma 2 viral oncogene homolog and epidermal growth factor receptor gene mutations.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Thoracic Medical Oncology Peking University Cancer Hospital & Institute Beijing China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Thoracic Medical Oncology Peking University Cancer Hospital & Institute Beijing China.
authors.forename: Hua
authors.initials: H
authors.lastname: Bai
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Thoracic Medical Oncology Peking University Cancer Hospital & Institute Beijing China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Yang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Thoracic Medical Oncology Peking University Cancer Hospital & Institute Beijing China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Thoracic Medical Oncology Peking University Cancer Hospital & Institute Beijing China.
authors.forename: Tongtong
authors.initials: T
authors.lastname: An
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Thoracic Medical Oncology Peking University Cancer Hospital & Institute Beijing China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Thoracic Medical Oncology Peking University Cancer Hospital & Institute Beijing China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
keywords: Advanced lung adenocarcinoma; EGFR mutation; EGFR‐TKI therapy; KRAS mutation; concurrent mutation
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