| Objective: To retrospectively analyze the efficacy,safety,and related factors of immune checkpoint inhibitors(ICIs),i.e.,Sintilimab,Camrelizumab,and Tislelizumab,combined with chemotherapy in treating patients with advanced non-small cell lung cancer(a NSCLC).Methods: A retrospective analysis was conducted on 97 a NSCLC patients without driver gene mutations at Northern Jiangsu People’s Hospital from January 2019 to June2022.Among them were 44 squamous cell carcinoma cases and 53 adenocarcinoma cases.All patients received ICIs treatment.Based on the type of ICI treatment they received,patients were divided into three groups: the Sintilimab group(37 cases),the Camrelizumab group(35 cases),and the Tislelizumab group(25 cases).Based on the presence of brain metastases,patients were divided into the brain metastasis(BM)group(11 cases)and the non-brain metastasis group(86 cases).Based on the modality of ICI treatments,patients were divided into the first-line treatment group(97 cases),the post-progression cross-line treatment group(30 cases),and the second-line treatment group(26 cases),and the difference in therapeutic effect between the cross-line treatment group and the second-line treatment group was analyzed.Based on the PD-L1 testing with tumor cell proportion score(TPS)≥ 1% as the cutoff,patients were divided into the PD-L1 positive group(26 cases)and the unknown PD-L1 expression group(71 cases).Based on the level of the lung immune prognostic index(LIPI)score,patients were classified into the good group(42 cases),the intermediate group(36 cases),and the poor group(19 cases).The primary endpoints of the study were progression-free survival(PFS)and overall survival(OS),and the secondary endpoints were objective response rate(ORR)and disease control rate(DCR).The therapeutic efficacy was evaluated using the Immune Response Evaluation Criteria in Solid Tumors(i RECIST),and the drug toxicity and adverse reactions were evaluated using the National Cancer Institute’s Common Terminology Criteria for Adverse Events(NCI-CTCAE 5.0).Survival curves were drawn using the Kaplan-Meier method,and Cox proportional hazards regression model was used to perform univariate and multivariate analyses to determine the factors influencing the prognosis,with a p < 0.05 indicating statistical significance.Results: 1.All patients were included in the efficacy evaluation.Their median PFS and OS for the entire group were 12.73 months and 20.83 months,respectively,and their ORR and DCR were 53.6% and 93.8%,respectively.2.Analyses of the impacts of these three different ICIs combined with chemotherapy on patients’ prognosis revealed no statistically significant differences in PFS,OS,ORR,and DCR among the three groups,with the median PFS being 13.30 months,12.73 months,and 10.97 months for patients in the Sintilimab,Camrelizumab,and Tislelizumab groups,respectively(p=0.322),the median OS being 24.17 months,21.87 months,and 18.17 months,respectively(p=0.315),the ORR being 54.3%,54.1%,and 52.0%,respectively(p=0.982),and the DCR being 91.4%,94.6%,and 96.0%,respectively(p=0.757).3.Prognosis analysis of patients with different histological subtypes showed no statistically significant difference in PFS,OS,ORR,and DCR between patients with squamous cell carcinoma and patients with adenocarcinoma,with the median PFS being15.33 months and 12.17 months for patients with squamous cell carcinoma and patients with adenocarcinoma(p=0.601),respectively,the median OS being 20.83 months and21.87 months(p=0.705),the ORR being 59.1% and 49.0%(p=0.414),and the DCR being 93.2% and 94.3%(p=1.000),respectively.4.Prognosis analysis of patients with and without brain metastases showed that the median OS was significantly different between patients without brain metastases and patients with brain metastases,being 21.87 months and 13.73 months,respectively(p=0.043).However,the median PFS,ORR,and DCR were not significantly different,being 13.13 months and 7.60 months for PFS(p=0.055),55.8% and 36.4% for ORR(p=0.337),and 95.3% and 81.8% for DCR(p=0.137),respectively.5.Comparison of the prognosis between different groups revealed that the median PFS of patients receiving cross-line treatment and second-line treatment was 6.83 months and 4.46 months(p=0.042),the ORR was 16.7% and 7.7%(p=0.431),and DCR was 70.0% and 50.0%(p=0.172),respectively,only showing statistically significant difference in PFS between the two groups.6.Analyses of the significance of PD-L1 detection under combination therapy showed that the median PFS of patients with PD-L1 positive and PD-L1 with unknown expression was 12.60 months and 12.73 months(p=0.238),the median OS was 22.13 months and 20.03 months(p=0.656),the ORR was 65.4% and 49.3%(p=0.119),and the DCR was 100% and 91.6%(p=0.187),respectively,all showing no significant differences.7.Analysis of the relationship between LIPI and the prognosis of immunotherapy showed that the median PFS of patients in the good group,intermediate group,and poor group was 15.33 months,12.73 months,and 8.30 months(p=0.005),and the median OS was 25.37 months,20.03 months,and 14.47 months,(p<0.001),respectively,showing statistically significant difference.In addition,the ORR was 64.3%,50.0%,and 36.8%(p=0.119),and the DCR was 97.6%,94.4%,and 84.2%(p =0.138),respectively,showing no significant difference.8.Univariate and multivariate analysis of PFS and OS using Cox regression showed that ECOG score(p<0.001)and LIPI score(p=0.001)were independent prognostic factors for PFS,and ECOG score(p<0.001),brain metastasis(p=0.038)and LIPI score(p<0.001)were independent prognostic factors for OS.9.Safety analysis of ICIs showed that 82(84.5%)patients experienced treatment-related adverse events(TRAEs),45(46.4%)patients had immune-related adverse events(ir AEs),five(5.2%)patients had grade 3-4 ir AEs,three patients had reactive cutaneous capillary endothelial proliferation(RCCEP),one patient had immune-mediated pneumonia,and one patient had abnormal liver and kidney functions.No grade 5 TRAEs occurred in all patients.Conclusions: 1.The efficacy of three ICIs combined with chemotherapy in the first-line treatment of driver gene-negative a NSCLC patients was similar,and regardless of PD-L1 expression status or squamous cell carcinoma/adenocarcinoma,there was no significant difference in the efficacy of the three ICIs combined with chemotherapy based on patients’ PFS and OS.The presence of brain metastases was one of the important factors affecting the efficacy of combined immunotherapy and chemotherapy.2.Based on the availability and economy of ICIs,cross-line therapy has certain clinical values.3.LIPI,as a predictive marker for the efficacy of immunotherapy,may predict which patients cannot benefit from immunotherapy in advance.4.In terms of safety,except for the higher incidence of RCCEP caused by Camrelizumab,there was no significant difference in the incidence of ir AEs. |
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