Efficacy And Safety Analyses Of Anlotinib Combined With Immune Checkpoint Inhibitors As The Late-line Treatment Of Advanced Non-small-cell Lung Cancer

Background and objective: Lung cancer ranks first among malignant tumors in China in terms of incidence and mortality,with non-small cell lung cancer(NSCLC)accounting for approximately 85% of all lung cancer cases.Most patients do not show any signs of tension at the onset of their condition,making it easy to misdiagnose the condition and miss the opportunity to undergo radical surgery at an early stage.Despite the fact that advanced NSCLC first-line and second-line treatments include chemotherapy,targeted therapy,immunotherapy,and radiotherapy,recurrence,and metastasis will occur eventually and limitied treatmentoption for the late-line.Although the ALTER0303 study confirmed that anlotinib has satisfactory efficacy in late-line treatment in patients with advanced NSCLC,there is no uniform standard for late-line in advanced NSCLC,and there are few studies on predicting efficacy,therefore explorations of new treatment options and markers are necessary.Extensive analysis of research showed that anlotinib combined with immune checkpoint inhibitors(ICIs)was effective in solid tumors,and further analysis revealed that peripheral blood markers neutrophil-to-lymphocyte(NLR)and platelet-to-lymphocyte(PLR)were independent risk factors affecting PFS.This retrospective study aimed to explore the efficacy and safety of anlotinib combined with ICIs as later-line treatment for advanced NSCLC and to analyze the effect of peripheral blood markers NLR and PLR on PFS.Methods: The clinical data of patients with advanced non-small lung cancer who were treated with ICIs with or without anlotinib in the First Affiliated Hospital of Nanchang University from May 2019 to May 2022 were retrospectively collected.A comparison of the effectiveness of combination therapies was performed based on the hematological indicators NLR and PLR,as well as the effects of these indicators on efficacy.SPSS 25.0 was used to statistically analyze the data,and the counting data was expressed in(%),the survival curve was plotted by Kaplan-Meier and compared between groups by rank sum test.The ROC curve obtains the best cut-off values of NLR and PLR.Univariate and multivariate COX regression analysis explores clinical factors associated with progression-free survival(PFS).The evaluation criteria for adverse effects are based on the National Cancer Institute Common Adverse Event Evaluation Criteria Version 4.0.Outcome observations:progression-free survival(PFS),overall survival(OS),objective response rate(ORR),disease control rate(DCR).Results: This study included 61 patients with a median age of 59 years.The short-term efficacy analysis showed that the ORR of the anlotinib group and anlotinib plus ICIs group was 17.8% and 39.4%,the DCR was 78.5% and 90.9%,both the ORR and DCR were not statistically significant(P = 0.066,P = 0.176).Survival analysis showed that the anlotinib plus ICIs had longer PFS(7.0 vs 4.0 months,P =0.035)and OS(19.0 vs 12.0,P = 0.047),compared with the anlotinib group.Adverse reactions are mainly manifested as fatigue,loss of appetite,hypertension,decreased white blood cell count,anemia,decresased platelet count,abnormal transaminase,high-density lipoproteinemia,hypercholesterolemia,increased creatinine,hypoalbuminemia,elevated alkaline phosphatase,rash,hand-foot syndrome and oral mucositis etc.The most common adverse reactions were hypertriglyceridemia(45.9%),anemia(44.3%),and hypertension(37.7%);Overall adverse effects are controllable.Univariate results of the overall population showed that pathological type(P = 0.015),metastatic sites(P = 0.033),therapy(P = 0.047),pre-treatment NLR(P = 0.011),pre-treatment PLR(P = 0.007),post-treatment NLR(P = 0.007),post-treatment PLR(P = 0.004)were factors affecting PFS,and further multivariate analysis showed that pathological type(P = 0.015)was an independent risk factor for PFS.Conclusion: Anlotinib plus ICIs therapy has certain advantages in efficacy and safety over anlotinib monotherapy as the late-line treatment of patients with advanced NSCLC,and the overall safety is controllable.Univariate analysis showed that pathological type,metastatic sites,therapy,pre-and post-treatment NLR,and preand post-treatment PLR were factors affecting PFS,which had a certain reference for the selection of patients.Pathologic type is an independent risk factor for PFS.Anlotinib in combination with ICIs as third-line or further treatment may be a good treatment option for paitents with advanced NSCLC.