摘要Objective:Chemotherapy-based regimens remain the standard first-and second-line treatment options for patients with driver gene-negative non-small cell lung cancer(NSCLC).However,in real-world settings,certain patients cannot tolerate chemotherapy or opt to decline it.Immune checkpoint inhibitors(ICIs)constitute the preferred chemotherapy-free alternative.To enhance patient prognosis,this study aimed to examine the efficacy of ICIs combined with anlotinib in real-world scenarios.Methods:This prospective,multicenter,real-world study evaluated the efficacy and safety of ICIs combined with anlotinib in patients with advanced NSCLC.Patients undergoing first-or second-line treatment were enrolled.The primary endpoint was progression-free survival(PFS),while the secondary endpoints included overall survival(OS),objective response rate(ORR),disease control rate(DCR),and safety.Results:In total,242 patients were enrolled from 28 centers.The median PFS for the entire cohort was 7.8[95％confidence interval(95％CI),7.0-9.5]months,OS events occurred in 112(46.3％)patients,with a current median OS of 17.0(95％CI,15.1-19.4)months.The ORR and DCR were 36.0％(95％CI,30.2％-42.2％)and 97.9％(95％CI,95.3％-99.1％),respectively.The median PFS was 9.8(95％CI,7.4-12.5)months for first-line therapy and 6.9(95％CI,6.0-8.3)months for second-line therapy.Treatment-related adverse events(AEs)occurred in 198(81.8％)patients,with grade 3-4 AEs reported in 22(9.1％)patients.Conclusions:This multicenter,real-world study demonstrates that the anlotinib-ICI combination regimen exhibits clinically meaningful efficacy and tolerability as a chemotherapy-free alternative for advanced NSCLC,offering viable evidence to guide treatment for patients who are unsuitable for conventional chemotherapy.