Analysis Of The Efficacy And Safety Of Immune Checkpoint Inhibitors In The Treatment Of Advanced Non-small Cell Lung Cancer

ObjectivesThe purpose of this study is to evaluate the efficacy and adverse reactions of ICIs in patients with advanced non-small cell lung cancer(NSCLC),we analyze the clinical and pathological characteristics and other related factors that may affect the efficacy,and provide reference for clinical screening of the best beneficiaries to achieve precise immunotherapy.MethodsWe retrospectively analyzed patients with stage IIIB-IV NSCLC who were treated with ICIs in Shaanxi Cancer Hospital from January 2019 to October 2020.We collected gender,age,smoking history,body mass index(BMI),ECOG score,lesion location,malignant pleural effusion(MPE),distant organ metastasis,TNM staging,history of hepatitis,high sensitivity C-reactive protein(hs-CRP),Histological type,degree of tumor differentiation,PD-L1 expression status,gene mutation status,treatment plan,number of treatment lines,adverse events.We calculated the granular-to-lymphocyte ratio(NLR),platelet/lymphocyte ratio(PLR),immune inflammation index(SII)and other inflammation complex indicators.We evaluated the efficacy according to the RECIST1.1 standard,and followed-up regularly until the disease progress.The ROC curve was used to determine the optimal cut-off value of the inflammation indicators NLR,PLR,SII and hs-CRP to predict the patient’s progression free survival(PFS).We divided the patients into high-level NLR/PLR/SII/hs-CRP group and low-level NLR/PLR/SII/hs-CRP group according to the optimal cut-off value.All data were analyzed using SPSS 26.0 and Graph Pad Prism 8.0 statistical software.Kaplan-Meier method was used to conduct univariate analysis and COX proportional hazards regression model multivariate analysis of independent risk factors affecting the prognosis of patients.P<0.05 was considered statistically significant.Results1.Among 106 patients,the overall objective response rate(ORR)was 35.8%(38/106);the ORR of ICIs single-agent first-line treatment was 60%(3/5),ICIs single-agent second-line ORR was 36.4%(4/11);ICIs single-agent third-line and above ORR was 22.2%(2/9).The ORR of ICIs combined with first-line chemotherapy was 45.2%(19/42),the ORR of ICIs combined with second-line chemotherapy was 35%(7/20),and the ORR of ICIs combined with third-line chemotherapy and above was 25%(3/12).2.Among 106 patients,the overall m PFS was 10.0 months.Among them,the m PFS of ICIs monotherapy first-line treatment was not reached;the second-line m PFS of ICIs monotherapy was 10.0 months;the m PFS of third-line and above was 5.0 months.ICIs combined with chemotherapy for first-line m PFS was 14.0 months;ICIs combined with chemotherapy for second-line m PFS was 10.0 months,and third-line and above m PFS was 5.0months.3.Univariate analysis showed: we found ECOG score ≥ 2 points,combined with MPE,with distant organ metastasis,combined with liver metastasis,high levels of inflammation indicators(NLR,PLR,SII,hs-CRP),third-line and above treatments and ICIs had negative effects correlation(P<0.05),while gender,age,smoking history,BMI,lesion location,lymph node metastasis,history of hepatitis,histological type,degree of tumor differentiation,treatment plan and ICIs treatment efficacy were not correlated(P>0.05).Multivariate analysis showed that the combination of MPE,high-level hs-CRP,third-line and above treatment before ICIs treatment were independent related factors that affected the efficacy of ICIs treatment(P<0.05).4.Among 106 patients,50%(53/106)of the patients underwent PD-L1 expression status detection.The median PFS of patients with high PD-L1 expression(PD-L1 expression ≥50%)was 7.0 months longer than that of patients with low PD-L1 expression(PD-L1 expression1-49%)(14.0 months vs 7.0 months,P=0.015).5.A total of 8 patients with EGFR mutations were resistant to EGFR-TKI,m PFS treated with ICIs for 5.0 months(95%CI: 1.5-8.5).6.Among 106 patients,49.9% had immune-related adverse events(ir AEs)of any grade.The most common ir AEs were skin capillary hyperplasia(15.1%,16/106),hypothyroidism(13.2%,14/106),hyperthyroidism(7.5%,8/106),immune-related pneumonia(6.6 %,7/106),immune-related hepatitis(3.8%,4/106),rash(1.9%,2/106),immune-related colitis(0.9%,1/106)and immune-related myocarditis(0.9%,1/106).Among them,skin capillary hyperplasia was all seen in patients who used carrelizumab,and other adverse reactions could be seen in different types of ICIs.Most ir AEs were of grade G1-G2(49%),and only one case of grade G3 pneumonia occurred.No G4 ir AEs were found.Conclusions1.Patients with advanced NSCLC who choosed ICIs for third-line and above might still benefit;patients with EGFR mutations who were resistant to EGFR-TKI therapy might benefit from treatment with ICIs.2.High ECOG score,MPE,distant organ metastasis,liver metastasis,high levels of inflammation indicators(NLR,PLR,SII,hs-CRP),third-line and above treatments had a certain correlation with the poor efficacy of ICIs,which might predict the efficacy of ICIs treatment.3.In this study,we found that skin capillary hyperplasia had a higher incidence of ir AEs,all of which found in carrelizumab,while other ir AEs could be found in different types of ICIs.