Clinical Study Of Anlotinib Combined With Pemetrexed In The Maintenance Treatment Of Advanced Non-Small Cell Lung Cancer Without Driver Gene Mutation

Objective:We aim to assess the clinical efficacy and safety of Anlotinib combined with Pemetrexed in the maintenance treatment of advanced non driver gene mutation,non-squamous,and non-small cell lung cancer after first-line platinum containing dual drug chemotherapy.Methods:A total of 33 patients who were diagnosed with advanced non-squamous non-small cell lung cancer without driver gene mutation in Qinghai University Affiliated Hospital from January 1,2018 to January 1,2021,were included in this study.After 4-6 cycles of first-line platinum containing dual drug chemotherapy,their disease was-evaluated to be complete remission,partial remission or stable disease.They were randomised into three groups:1)10 patients in the Anlotinib combined with Pemetrexed group were given Anlotinib 12 mg orally once a day,for two weeks,stopped for one week,Pemetrexed 500 mg/m~2,intravenously on the first day and repeated every three weeks;2)11 patients in the Anlotinib group were given Anlotinib 12 mg orally once a day,for two weeks,stopped for one week,and repeated every three weeks;3)12 patients in Pemetrexed group were given Pemetrexed 500 mg/m~2 intravenously on the first day and repeated every three weeks;All the three groups were treated until the disease progressed or could not be tolerated.The progression free survival,objective remission rate,disease control rate and adverse reactions of the three groups were compared.SPSS 26.0 software was used to statistically analyze the patient data.The measurement data were described by relative numbers.The composition ratio between groups was calculated by chi square test.And the rate between groups was compared by chi square test or Fisher exact probability method.The survival data were described by median survival time.And the survival analysis was performed by log-rank test.Statistically significant P values were indicated as P<0.05.Results:Progression-free survival was 8.6,6.4,and 4.5 months in patients with advanced non-squamous non-small cell lung cancer without driver gene mutations treated with Anlotinib combined with Pemetrexed versus Anlotinib and Pemetrexed,respectively(P<0.001).The objective response rates in the three groups were 20%,9.09%,and 8.33%,respectively(P>0.05),and the disease control rates in the three groups were 90%,81.81%,and 74.99%,respectively(P>0.05).The adverse reactions in the three groups were tolerable.There was 1 case of grade 3 hypertension in the Anlotinib combined with Pemetrexed group,1 case of grade 3 hypertension and 1case of grade 3 hand-foot-skin reaction in the Anlotinib group.There was no grade 3adverse reaction in the Pemetrexed group.There was no grade 4 or higher adverse reaction in the three groups.There was no significant difference in the total adverse reactions and grade 3 or higher adverse reactions among the three groups(P>0.05).Further,according to the rank order of the incidence rate of adverse reactions in the three groups,fatigue ranked first,hypertension,loss of appetite and vomiting ranked second,leukopenia and thrombocytopenia ranked third in the rank order in the Anlotinib combined with Pemetrexed group;hypertension ranked first,fatigue ranked second,hand-foot-skin reactions,loss of appetite,cough and diarrhea ranked third in the rank order in the Anlotinib group;loss of appetite and vomiting ranked first,fatigue,leukopenia and thrombocytopenia ranked second,and cough ranked third in the rank order in the rank order in the Pemetrexed group.Conclusion:Comparing to the maintenance therapy using Anlotinib or pemetrexed,Anlotinib combined with Pemetrexed can prolong the progression-free survival and benefit the survival of patients with advanced non-squamous non-small cell lung cancer without driver gene mutation after first-line platinum-based doublet chemotherapy.And the adverse reactions were tolerable.