Abstract: 【Abstract】 Objective To investigate the type and severity of skin adverse reactions induced by afatinib in the treatment of lung cancer, and to analyze their correlation with anti-lung cancer efficacy. Methods A case-case-control study was conducted on lung cancer patients treated with afatinib in ZhongDa Hospital, Southeast University from December 2016 to January 2018. The type and severity of skin adverse reactions were evaluated in 76 patients with lung cancer based on the National Cancer Institute-Common Terminology Criteria for Adverse Events （NCI-CTCAE） Version 4.0, and these patients were divided into 3 groups according to the severity of skin lesions, including grade-0, -1, and -2/3 groups. The patients underwent chest computed tomography （CT） examination every 3 months, and the tumor response to afatinib was evaluated according to the Response Evaluation Criteria in Solid Tumors （RECIST）. Anti-lung cancer efficacy of afatinib was compared among the patients with different grades of skin lesions by using the Kruskal-wallis H rank sum test. Results After treatment with afatinib, 44 of the 76 patients with lung cancer achieved stable condition or partial remission, and 32 experienced disease progression. Skin adverse reactions occurred in 69 patients, and manifested as acneiform lesions in 42 （55.3%） patients, paronychia in 35 （46.1%） , mucosal erosions in 30 （39%）, hair changes in 8 （10.5%）, and hand-foot syndrome in 6 （7.9%）. Improvement was achieved in 3, 7 and 34 cases in the grade-0, -1, and -2/3 groups （n = 7, 19 and 50 respectively）, respectively. There was a significant difference in the response rate among the 3 groups （χ2 = 6.117, P = 0.047）, and the response rate was significantly higher in the grade-1 and -2/3 groups than in the grade-0 group （both P < 0.001）, and higher in the grade-2/3 group than in the grade-1 group （P < 0.001）. Conclusion The treatment of lung cancer with afatinib can cause various types of skin lesions, such as acneiform lesions, paronychia, mucosal erosions, hair changes and hand-foot syndrome, and the higher the severity of the skin lesions, the more marked the anti-lung cancer efficacy of afatinib.

Key words: Drug toxicity, Receptor, epidermal growth factor, Biological agents, Acneiform eruptions, Paronychia, Afatinib