Wei He, Yan Zhang, Yu Xiong, Feng-juan Dai, Qing-xia Fan The Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China Background: The efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitors have been studied worldwide. However, there are few reports directly comparing the efficacy and safety between icotinib and docetaxel as second-line treatment in lung adenocarcinoma patients who have failed platinum-based chemotherapy. This article offers insight into this field.Methods: A total of 137 patients with stage III or IV lung adenocarcinoma who had progressed on first-line platinum-based therapies and received icotinib or docetaxel therapy between October 2011 and February 2013 were retrospectively reviewed. Patients in the icotinib group received oral icotinib at a dose of 125 mg tid, while patients in the docetaxel group received infusion docetaxel at a dose of 75 mg/m2 on day 1 of every 21 days (four to six cycles) until disease progression or unacceptable toxicity occurred after which best supportive care was given.Results: There was no statistically significant difference in the objective response rate (23.3% vs 12.5%, P=0.103), progression-free survival (121 days vs 106 days, P=0.083), and overall survival (307 days vs 254 days, P=0.070) between the two groups. As compared to the docetaxel group, the disease control rate (75.3% vs 54.7%, P=0.011) was significantly better in the icotinib group. In the icotinib group, the most common adverse events were rash (35.62%) and diarrhea (24.66%), whereas in the docetaxel group, elevation of transaminase (37.50%), leukopenia (50.00%), and anemia (54.69%) were the most common.Conclusion: Icotinib had similar efficacy and a lower adverse events rate in epidermal growth factor receptor-unselected patients as compared to docetaxel, thereby making it an effective second-line therapy option for lung adenocarcinoma. Keywords: icotinib, docetaxel, second-line therapy, lung adenocarcinoma, EGFR-TKIs