Meta Analysis Of The Effect Of TMB On The Prognosis Of NSCLC After Immunotherapy

Background:Lung cancer is one of the world’s high-risk tumors.According to the statistics of the World Health Organization,the number of people who died of lung cancer in2018 was about 1.76 million,accounting for 18.4% of all cancer deaths.The most common pathological type of lung cancer is NSCLC(non small cell lung cancer),and non-small cell lung cancer accounts for 80% to 85% of lung cancer.Non small cell lung cancer patients are easily ignored because of their early clinical symptoms,which are easily ignored.Generally,patients are found to be in hospital after they have cough up blood,cough for a long time and transfer symptoms.The treatment methods of NSCLC include surgical operation,chemical treatment,radiotherapy and targeted treatment.In recent years,immunocheckpoint inhibitors have been used Inhibitors(ICIS)has achieved good results in the treatment of NSCLC,which greatly improves the survival time and quality of life of patients with advanced NSCLC,and makes the treatment of NSCLC enter the era of immunotherapy;however,not all patients with NSCLC have reactions to PD-1 inhibitor / PD-L1 inhibitor treatment,only a few patients respond to ICI treatment There are reactions in the treatment.In recent years,as a predictor of the prognosis of NSCLC,tumor mutation load(TMB)is becoming more and more.This paper makes meta analysis on this,and discusses the prognosis of NSCLC by TMB,so as to provide evidence-based medical basis for clinical practice,and hope to have some guiding value for clinical practice.Objectives:The purpose of this study is to systematically study the effect of TMB on the prognosis of immunotherapy for NSCLC,so as to provide reference for clinical practice.Method:Pub Med,Cochrane Library,EMBASE,How Net and other databases were systematically searched.Three randomized controlled trials(RCTs)were included,Seven retrospective case-control trials and cohort studies were conducted.The risk ratio and 95% confidence interval of overall survival(OS)and progression free survival(PFS),objective response rate(ORR)and adverse reaction events were extracted from the studies.The data were analyzed by Revman 5.3 software.Results:(1)In 7 RS studies,we compared the prognosis of patients with high TMB and patients with low TMB in immunotherapy for non-small cell lung cancer(NSCLC)(A)In terms of objective response rate(ORR),the orr of high TMB group was higher than that of low TMB group,with statistical significance [or = 4.20,95% CI(2.33,7.57),P < 0.00001].(B)In terms of progression free survival(PFS),the PFS of high TMB group was significantly higher than that of low TMB Group [HR = 0.43,95% CI(0.34,0.55),P< 0.00001].(C)In terms of overall survival(OS),the results showed that the OS of high TMB group was higher than that of low TMB group,and the difference was statistically significant [HR = 0.53,95% CI(0.35,0.80),P = 0.003].(2)In three phase Ⅲ randomized controlled trials,we compared the prognosis of immunotherapy and chemotherapy in patients with high TMB(A)In terms of objective response rate(ORR),the results showed that the orr of immunotherapy in patients with high TMB was higher than that of chemotherapy in patients with high TMB [or = 2.56,95% CI(1.70,3.83),P < 0.00001].(B)In terms of progression free survival(PFS),the results showed that the progression free survival(PFS)of immunotherapy in patients with high TMB was higher than that of chemotherapy in patients with non-small cell lung cancer(NSCLC),and the difference was statistically significant [HR = 0.59,95% CI(0.47,0.75),P < 0.0001].(C)In terms of overall survival(OS),the results showed that there was no significant difference in OS between immunotherapy and chemotherapy for non-small cell lung cancer(NSCLC)patients with high TMB [HR = 0.72,95% CI(0.32,1.59),P = 0.41 > 0.05].(3)Subgroup analysis: in the checkmate-227 study,the effects of PD-L1 expression status(PD-L1 ≥ 1,PD-L1 < 1)on progression free survival were compared.The results showed that the progression free survival(PFS)of patients with high TMB treated with immunotherapy was higher than that of patients with high TMB treated with chemotherapy for non-small cell lung cancer(NSCLC),which was not related to the expression level of PD-L1,and the results were statistically significant [HR = 0.58,95% CI](0.43,0.78),P=0.0003].(4)Safety analysis:In three RCT studies(checkmate-026,checkmate-227,mytic),we conducted a meta-analysis of the related adverse events.The high-level adverse events(grade 3and grade 4)of immunotherapy on chemotherapy were found.The results showed that immunotherapy was lower than chemotherapy in grade 3 and grade 4 adverse events,and the difference was statistically significant [or = 0.46,95% CI(0.22,P <0.05),0.96),P=0.04]。 All three RCTs reported related death events.The results showed that there was no significant difference in death events between immunotherapy and chemotherapy [or = 1.22,95% CI(0.57,2.62),P = 0.61].Three RCT studies reported total adverse events,the results showed that the total adverse events of immunotherapy were lower than that of chemotherapy,the difference was statistically significant [or = 0.37,95% CI(0.17,0.77),P = 0.008].Conclusion:For non-small cell lung cancer(NSCLC),immunotherapy in patients with high TMB is more effective than that in patients with low TMB,immunotherapy in patients with high TMB is more effective and safer than chemotherapy in patients with high TMB,and immunotherapy in patients with high TMB has higher progression free survival(PFS)than chemotherapy in patients with high TMB.