Efficacy And Safety Of ICIs In Lung Cancer Patients With Concomitant ILD: A Meta-analysis Of Observational Studies

Objective:To compare the clinical outcomes and differences in the occurrence of immune-related pneumonia in lung cancer patients with and without interstitial lung disease(ILD)treated with immune checkpoint inhibitors(ICIs).Methods:Pubmed,Embase,Cochrane Library,and Web of Science databases were searched for published literature on the efficacy and safety of ICIs in patients with lung cancer combined with ILD from the date of database construction to December 10,2022.The quality of the included studies was assessed using the Newcastle Ottawa Scale(NOS).Two investigators selected the literature strictly according to inclusion and exclusion criteria,and data were extracted separately and independently,with decisions made after controversial discussions.The outcome indicators in terms of effectiveness included Progression-free survival(PFS),Overall survival(OS),Objective response rate(ORR),Disease control rate(DCR).PFS and OS were expressed as statistical effect sizes using hazard ratio(HR)and 95%confidence interval(95%CI);ORR and DCR were expressed as Odd ratio(OR)and 95%CI.The safety outcome indicator was the incidence rate of any grade and grade 3 or higher ICI-P.Statistical effect sizes were expressed using OR and 95%CI.Based on I~2 test was used to assess the heterogeneity between these studies.In addition,publication bias of included articles was estimated using funnel plots,Begg’s Test and Egger’s Test.Meta-analysis of data from the included studies was applied using Stata version 17.0 software and Review Manager 5.4software provided by the Cochrane Collaboration.Results:A total of 25 papers on the effectiveness or safety of ICIs in patients with lung cancer combined with ILD were included.Among them,12papers containing survival and efficacy data were included in the effectiveness analysis;25 papers containing ICI-P-related data were included in the safety analysis.For the survival index PFS,there was no significant difference between PFS in lung cancer patients with combined ILD treated with ICIs and those without combined ILD[HR=0.92,95%CI(0.76-1.10),P>0.05].For the survival index OS,there was also no significant difference in OS between lung cancer patients with combined ILD treated with ICIs and lung cancer patients without combined ILD[HR=1.01,95%CI(0.76-1.34),P>0.05].For the efficacy index ORR,the ORR of lung cancer patients with combined ILD treated with ICIs was significantly better than that of lung cancer patients without combined ILD,and the difference was statistically significant[OR=1.99,95%CI(1.33-2.97),P<0.05].For the efficacy index DCR,lung cancer patients with combined ILD treated with ICIs had significantly better DCR than those without combined,and the difference was statistically significant[OR=1.87,95%CI(1.20-2.93),P<0.05].Regarding safety,lung cancer patients with combined ILD treated with ICIs were statistically more likely to develop any grade ICI-P than lung cancer patients without combined ILD[OR=4.44,95%CI(3.62-5.45),P<0.005];they were also more likely to develop grade 3 or higher ICI-P,with a statistically significant difference[OR=3.66,95%CI(2.61-5.12),P<0.005].To further clarify the relationship between different HRCT staging and ICI-P in combined ILD before receiving ICIs,we performed a pooled analysis of 10 papers containing relevant data and found no significant differences in the incidence rate of any grade ICI-P among the 3 subtypes of probable UIP type&UIP type,indeterminate UIP type and NSIP type.Similarly,to clarify the relationship between the treatment with different types of ICIs and the occurrence of ICI-P in patients with combined ILD lung cancer,we performed a pooled analysis of 22 papers containing relevant data,and the results showed that there was no statistically significant difference between receiving PD-1 inhibitors and PD-L1 inhibitors.Conclusions:1.Patients with lung cancer with previous combined ILD treated with ICIs had significantly higher ORR and DCR in terms of efficacy indexes than those without combined ILD,but there was no difference in PFS and OS in terms of survival indexes.2.The risk of ICI-P was higher in lung cancer patients with previous combined ILD treated with ICIs than in those without.Subgroup analysis was performed and found that there was no difference in the%of ICI-P between different imaging staging of combined ILD and receiving different types of ICIs.