Efficacy And Safety Of Immunocheckpoint Inhibitor Combined With Chemotherapy In The Treatment Of Advanced Bladder Cancer

Objective: To systematically evaluate the efficacy and safety of immuno checkpoint inhibitor combined chemotherapy(immuno+chemotherapy group),immuno checkpoint inhibitor dual drug combination(dual immuno group)and immuno checkpoint inhibitor single drug group(single immuno group)compared with chemotherapy in patients with advanced bladder cancer,so as to provide Evidence-based medicine basis for clinical drug combination.Methods: In the first part,we searched Pub Med,Webofscience,CNKI and other databases with computers for Document retrieval and Randomized controlled trial in the Clinical Trials.gov database.The search time was from the establishment of the database to February 1,2023.The researchers screened the literature according to the established inclusion and exclusion criteria and used End Note20 reference Reference management software,collected the data of the included literature,and conducted literature quality evaluation and meta analysis through Rev Man5.4.1 software.The second part is a retrospective analysis of 45 patients with advanced bladder cancer who were admitted to our hospital from January 2018 to December 2022.All of them were confirmed as bladder urothelial cancer by pathological examination.Among them,15 patients received four cycles of combined chemotherapy with inhibitors at the immune checkpoint,and 30 patients received only four cycles of chemotherapy.The objective response rate,progression free survival period,adverse reactions,and risk factors affecting disease progression were compared between the two groups.Results: Meta analysis showed that compared with the chemotherapy group,the monoimmunization group had advantages in progression free survival(HR=1.33,95% CI:1.17-1.50,P<0.01),objective response rate(OR=0.42,95% CI: 0.35-0.50,P<0.01),and safety(OR=0.14,95% CI: 0.11-0.19,P<0.01),but there was no statistically significant difference in complete response rate between the two groups(OR=0.98,95% CI:0.74-1.31,P=0.91).Compared with the chemotherapy group,the immune plus chemotherapy group had advantages in overall survival(HR=0.85,95% CI: 0.74-0.96,P=0.01),progression free survival(HR=0.80,95% CI: 0.71-0.90,P=0.0003),objective response rate(OR=1.29,95% CI: 1.06-1.58,P=0.01),and complete response rate(OR=1.56,95% CI: 1.13-2.14,P=0.007);However,the immune+chemotherapy group is more prone to immune related adverse reactions(OR=1.57,95% CI: 1.05-2.36,P=0.03).There was no statistically significant difference in overall survival time(HR=0.91,95%CI: 0.74-1.13,P=0.41)and safety between the single and double immunization groups(OR=0.60,95% CI: 0.27-1.35,P=0.22).In the second part of the Case–control study,there was no significant difference between the two groups in age,gender,smoking history,T stage,N stage,M stage,and ECOG score(p>0.05),and there was no significant difference in the incidence of adverse reactions between the two groups(p>0.05).Four of the 15 patients in the Immunosuppressive drug combined chemotherapy group progressed;20 out of 30 patients in the chemotherapy group progressed.The median PFS of the Immunosuppressive drug combined chemotherapy group was not reached,the median observation time was 12.1(10.5-13.6)months,and the median PFS of the chemotherapy group was 10.9(9.6-12.4)months.Log rank analysis showed that the difference between the two groups was statistically significant(P<0.05).The univariate and multivariate Cox regression analysis of disease progress showed that the treatment scheme(immunization+chemotherapy)was a protective factor(OR=0.082,p<0.001),and age and TNM stage were risk factors.Conclusions: 1.Compared with the chemotherapy group,the Immunosuppressive drug monotherapy group has better objective response rate and safety,but has no obvious advantage in prolonging the total survival period and progression free survival period.2.Both meta-analysis and retrospective study analysis suggest that compared with the chemotherapy group,the immune checkpoint inhibitor combined with chemotherapy regimen has a better objective response rate and complete response rate,and can significantly prolong overall survival and progression free survival.3.There was no significant difference in overall survival and incidence of adverse reactions between the dual drug combination of immune checkpoint inhibitors and the single drug group of immune checkpoint inhibitors.