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

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.National Natural Sciences Foundation Key Program [81330062]; Education Ministry Innovative Research Team Program [IRT13003]; Peking University-Tsinghua University Joint Center for Life Sciences Clinical Investigator; National High Technology Research and Development Program 863 [SS2015AA020403]; Beijing Technology Project [Z141100000214013]; Center for Molecular and Translational Medicine (CMTM); Special Research Found for the Doctoral Program of Higher EducationSCI(E)PubMedARTICLEzlhuxi@163.com124-31