Efficacy And Safety Of Immunotherapy Versus Chemotherapy As Second-line Treatment On Esophageal Squamous Cell Carcinoma:Meta Analysis

BACKGROUNDAt pressent,the incidence of esophagus cancer is high.Within the globe,the morbidity of esophageal cancer was seventh and the death rate is sixth.Esophageal carcinoma’s pathology mainly consists of squamous carcinoma and adenocar-cinoa.In China,the proportion of ESCC has reached 90%.Most of the patients diagnosed esophageal cancer were late and have already lost operative opportunities.For these patients generally adopted multidisciplinary treatment such as radiotherapy,chemotherapy and surgery.However,the five years’ survival rate was only 30%-40%.Advanced ESCC first-line chemotherapy usually was selectsed taxanes,fluorouracil and platinum.When ESCC was progressive after the first-line chemotherapy,its treatment’s strategies were very finitude.Traditionally,second-line chemotherapy was limited to monotherapy,such as irinotecan,paclitaxel and docetaxel,whereas lacked sufficient evidence-based proof.In recent years,the research of Immune Checkpoint Inhibitors(ICIs)has been increasingly mature,and a variety of effective drugs have been developed.At present,the ICI has been widely used in tumors,for instance,gastric cancer,non-small cell lung cancer,malignant melanoma,kidney cancer.Additionnally,its second-line treatment in advanced ESCC is increasingly mature,showing beautiful clinical effects.This paper mainly was performed a Meta analysis for the clinical trials of ICI secondary treatment ESCC to assess the safety and efficacy of these drugs.ObjectiveThis study’s aim was to assess the efficacy and safety of ICI secondary treatment in ESCC comparative chemotherapy,and provided more evidences for clinical treatment.MethodsBy retrieving electronic databases such as PUMED,Cochrane Libraray and Embase.Using the keywords and free terms,the deadline was August 30,2020.This papers’ researchs all were prospective studies.The extractions included median oveall survival(m OS),median progressionfree time(m PFS),median survival Ration(MSR),median survival ration(MSR)and confidence interval(CI).Likewise,we exacted objective response rate(ORR),disease control rate(DCR)and confidence interval(CI).Moreover,we also exacted different PD-L1 expression,different age,various regions,different ECOG scores relative risk(RR)and confidence interval(CI).Additionally,we exacted the total number of any,above 3 or more adverse reactions and their confidence interval(CI).Time data event was analyzed by the risk ratio(HR)and its 95% confidence interval(CI).Bicategorized variables were evaluted throught the relative risk(RR)and 95% confidence interval(CI).The statistic software used was Stata.15.Results1.Efficacy evaluation:1).Relative to OS: Compared to the chemotherapy group,the MSR value was1.24,95% CI(1.15-1.34),P <0.001,statistically significant,immunotherapy can increase the OS time of 1.24 times.Immunotherapy can increase 12 Month OS,18 Month OS Rate and reduce the risk of OS death.2).As far as PFS: Compared to chemotherapy group,the value of MSR was 0.74,95% CI(0.48-1.05),the effect of immunotherapy was only 0.74 times the chemotherapy group.P <0.001,it has statistical significance,which showed that chemotherapy was superior to PFS time.3).In terms of ORR,DCR: The RR values of ORR and DCR were 1.66,95%CI(0.48,5.81),P = 0.426> 0.05;0.90,Ci95%(0.40,2.00),p = 0.790>0.05,repectively.There was no statistical significance,needed more clinical evidence to turn out.2.Safety evaluation:1).Immunotherapy adverse reactions: The overall probability of any level treatment related adverse events was 77.2%(95% CI: 55.8%-98.7%),the incidence of ≥3 adverse reactions was 18.3%.(95% CI: 14.9%-21.7%),the death incident associated with immunotherapy was 3.8%(95% CI: 1.9%-5.6%).In addition,the incidence of termination treatment about immunotherapy was 9.0%(95% CI:5.1%-12.9%).2).TRAES ≥ 3: The RR was 0.37(95% CI: 0.22,0.63;P <0.001),both difference has statistical significant,indicating that the incidence of high-level adverse reactions in immunotherapy was lower than chemotherapy.3.Subgroup analysis:1).Packet analysis in different PD-L1 expression levels: Compared to chemotherapy,PD-L1 <1%,PD-L1 ≥1% and PD-L1 ≥ 10% MSR were 0.16,95% CI(0.03,0.29),P <0.001;0.34,95% CI(0.24,0.44),P <0.001;0.33,95% Ci(0.20,0.46),P <0.001,respectively.Regardless of the level of PD-L1 expression,immunotherapy could extend ESCC patients survival period.2).subgroup analysis of different ECGO scores,age and region: ECGO = 0 HR was 0.91,95% CI(0.69,1.19),p = 0.487> 0.05;ECGO = 1 HR was 0.65,95% CI(0.55,0.77)P <0.01.Age <65 HR was 0.71,95%(0.59,0.86),P <0.01,and age> 65 was 0.74,95%(0.52,1.05),p = 0.091> 0.05.The Asian group patients HR was0.78,95%(0.62,0.98),p = 0.03 <0.05;Non-Asian HR was 0.63,95%(0.20,1.96),p= 0.426> 0.05.Immunotherapy was more beneficial to lower ECGO scores,young and Asian patients,but these were based on existing data,required more clinical proof to prove.Conclusion1.Immunosuppressors can extend OS of patients in advanced ESCC,and can benefit for a long time,and continue to mitigate the time than chemotherapy.However,PFS does not seem to be better than chemotherapy.2.How is the level of expression without PD-L1,ESCC patients can benefit from second-line treatment of immune preparations,suggesting a certain reference value in clinical practice,but still requires more evidence to support.3.Immunotherapy is more beneficial to ECGO scores,patients with age,Asian groups,but this is based on existing data,and more clinical data is required to prove.