e14050 Background: EGFR gene mutations were discovered in some of NSCLC patients. Two major EGFR mutations include 19del and L858R. These mutations account for more than 90% of all mutations related to EGFR TKIs sensitivity. Icotinib, an EGFR TKI, showed equivalent response rates and better tolerability compared with gefitinib, double blind trial (ICOGEN) with advanced NSCLC previously treated in China. In addition, other uncommon mutations have been identified. The efficacy of icotinib in patients harboring these mutations to icotinib is still unknown. This study investigated the efficacy of icotinib in patients carrying G719X/E709X/G724S in exon 18, S768I/20 insertions/T790M/V769M in exon 20 and L861Q/L833F in exon 21. Methods: Retrospectively analysed 24 cases of 18 exon, 58 cases of 20exon and 17 cases of 21 exon uncommon mutation NSCLC patients until the progress of the disease or the emergence of the side effects and clinical efficacy was observed after months followed-up. Results: 99 patients with G719X/E709X/G724S/S768I/20 insertions/T790M/V769M/ L861Q/L833F mutations were enrolled. The patient response rate and disease control rate were 31.58%, 66.66%, 0, 25.00%, 11.11%, 4.76%, 0%, 23.53%, 0% and 73.68%, 66.66%, 100%, 80.00%, 44.44%, 47.62%, 100%, 64.71%, 100%, respectively. The mPFS were 2.7 months, respectively. Patients with L833F mutation manifested the longest mPFS(4.2 months), followed by those with G724S mutation(3.5 months), S768I and V769M(3.2 months), E709X(3.1 months), G719X(2.8 months), L861Q(2.2 months), exon 20 insertions(1.9 months) and T790M(1.6 months). Patients with complex mutations show a better PFS than those with single mutations(G719X mutations 3.3 months vs 2.6 months, P = 0.029; E709X 7.2 months vs 2.7 months, P = 0.225; S768I mutations 2.2 months vs 3.3months, P = 0.174; T790M 2.45 months vs 2.9 months, P = 0.845; L861Q mutations 2.1 months vs 5.6 months, P = 0.065 ).Conclusions: Icotinib is less effective in patients with uncommon mutations than in those with common mutations. Patients with complex mutations benefited more from icotinib than those with single mutations.