Lung cancer is the second mostly diagnosed tumor and may be the leading reason behind cancer-related loss of life in men and women [1]. success (PFS) in addition to better quality-of-life ratings [5-9]. As a result EGFR TKIs have grown to be the most well-liked first-line treatment for NSCLC sufferers with EGFR mutations. Among sufferers with advanced NSCLC 10 of Caucasian sufferers and around 50% of Asian sufferers have got EGFR mutations [10 11 Although EGFR TKIs possess improved final results for sufferers with EGFR mutations [7 9 few research on optimum second-line remedies including second-line cytotoxic chemotherapy after failing of first-line EGFR TKI have already been reported. Where administration of cytotoxic chemotherapy after TKI failing is being prepared platinum-based doublet chemotherapy is highly recommended because the first-line cytotoxic treatment. Nevertheless since cytotoxic chemotherapy has been 12772-57-5 manufacture used being a second-line treatment after EGFR TKI failing a singlet agent such as for example docetaxel or pemetrexed may be used. Although there is absolutely no strong supporting proof current guidelines recommend use of platinum-based doublet chemotherapy after failure of first-line EGFR TKI [12]. To date no randomized prospective studies have been reported and the use of platinum-based doublet or singlet cytotoxic chemotherapy remains controversial. The purpose of this study was to compare the clinical efficacy of singlet pemetrexed with the efficacy of platinumbased doublets used as second-line therapy after failure of EGFR TKI used as first-line therapy for NSCLC patients with EGFR mutations. Materials and Methods 1 Patients We performed a retrospective screening of 314 patients with advanced NSCLC and EGFR mutations who were seen at Seoul National University Hospital (SNUH) Seoul National University Bundang Hospital (SNUBH) and Seoul National University Boramae 12772-57-5 manufacture Medical Center (SNU-BMC) from January 2006 to April 2014. The inclusion criteria were as follows: (1) activating EGFR mutations consisting of microdeletion 12772-57-5 manufacture in exon 19 or an L858R point mutation in exon 21 (2) all of the study patients had received first-line therapy using palliative EGFR TKI (gefitinib or erlotinib) and (3) all patients had failed first-line EGFR TKI treatment. A total of 83 patients were enrolled in the study. This study was approved by the Institutional Review Boards (IRBs) of SNUH SNUBH and SNU-BMC (SNUH IRB No. 1404-080-564; SNUBH IRB No. B-1404/246-405; SNU-BMC IRB No. 16-2014-43). The Declaration of Helsinki tips for biomedical analysis involving human topics were also implemented. 2 Data collection The sufferers’ medical information were used to get information on the next: health background of tumor histopathological profile from the tumor treatment history and imaging studies. The EGFR gene mutations were determined using a 12772-57-5 manufacture direct sequencing method [13 14 Patients underwent baseline computed tomography at the beginning of second-line cytotoxic chemotherapy routine chest radiography every 3-4 weeks and computed tomography every 2-3 cycles of chemotherapy. Evaluation of treatment response was based on the Response Evaluation Criteria in Solid Tumors (RECIST) [15]. Patients achieving complete response and partial response were considered to be responders. The primary endpoint was PFS after second-line chemotherapy. Secondary endpoints were the RR after second-line chemotherapy and overall survival (OS). 3 Statistical analysis The baseline characteristics of the study populace were analyzed using descriptive statistics. PFS of second-line chemotherapy was calculated from the date of initiation of second-line chemotherapy to the date of cancer progression or any cause of death. PFS was also calculated from the Selp date of initiation of first-line TKI. OS for second-line chemotherapy was measured from the date of initiation of second-line chemotherapy to the date of death from any cause. PFS and OS were estimated using Kaplan-Meier analysis and the difference between the survival curves of the treatment groups was tested using the log-rank test. Univariate analysis and multivariate analysis were performed using the Coxregression proportional hazards model..