Abstract In this study,we investigated a the combination of osimertinib/ gefitinib/ erlotinib with cytotoxic chemotherapy for EGFR-mutated positive lung adenocarcinoma patients in long-term survival outcomes. Method We enrolled Ⅲb-IV stage lung adenocarcinoma patients，Patients receiving standard Osimertinib,Gefitinib,Erlotinip alone treatment and Osimertinib,Gefitinib and Erlotinip with cytotoxic chemotherapy were retrospectively reviewed. Result First generation Chemical-TKItherapy PFS vs First generation TKI therapy alone PFS.P<0.05.Mean Survival Time（MST）22.00 month VS 16.00.OS P<0.05. MST 32.00 month VS 28.00.Third generation Chemical-TKItherapy PFS vs Third generation TKI therapy alone PFS.P<0.001.MST 40.00 month VS 26.66. OS P<0.05.MST 48.00 month VS 36.00.First-Third generation Chemical-TKItherapy PFS vs First-Third generation TKI therapy alone PFS.P<0.001.(MST)28.00 monthVS 17.00.OS P<0.001.MST 41,00 month.VS 29.00.Cox regression models showed a significant prognostic factors for OS were old age (55-69 years) (HR 0.49 [0.28–0.89], p < 0.02) and gene mutation (Positive) (HR  0.15 [0.07–0.29], p < 0.05),First add third generationTKI with chemicaltherapy (HR 0.56 [0.35–0.89], p < 0.02). Conclusion The results obtained under real-life conditions add to our understanding of the benefits and risks of First-Third generation EGFR inhibitor combined with cytotoxic chemotherapy in routine clinical practice.