A Real-world Study Of Immunotherapy For Urothelial Carcinoma

Objective:One of the most prevalent urogenital system cancers,urothelial carcinoma(UC),can develop in any part of the urinary tract,including the renal pelvis,ureter,bladder,and urethra.Presently,advanced urothelial carcinoma is primarily treated with platinum-based chemotherapy.Due of inhibitory side effects brought on by chemotherapy medications and treatment delays in non-responders,nearly half of the patients are ineligible for chemotherapy.It is important to note that immunotherapy for tumors has advanced quickly in recent years and has achieved amazing success in the treatment of malignancies like melanoma,lung cancer,and other types of tumors.Immune checkpoint inhibitors(ICIs)represented by PD-1 and PD-L1 are currently approved for second-line treatment of patients with advanced bladder cancer and for first-line treatment of patients who are PD-L1 positive and ineligible for platinum-based chemotherapy,offering novel approaches for the management of urothelial cancer.This study looked at clinical characteristics associated with prognosis to provide guidance for clinical medication and retrospectively assessed the clinical efficacy and safety of using immune checkpoint inhibitors in the treatment of locally progressed and metastatic UC.Method:From August 2018 to August 2022,50 patients with locally advanced or metastatic UC who used ICIs were admitted to our hospital.These patients were monitored until the patient’s disease progressed,they passed away,or the follow-up deadline passed on December 15,2022.Overall survival(OS)and progression-free survival(PFS)were the main study objectives,and disease control rate(DCR)and objective response rate(ORR)served as its secondary endpoints.Adverse events were assessed and graded according to the Common Terminology Criteria For Adverse Events Versions 5.0 of the National Cancer Institute(NCI)(CTC-AE 5.0).The SPSS 26.0 program was utilized to conduct the statistical analysis.The Kaplan-Meier method was used to determine the median PFS and OS,and the Log-rank test was used to compare them.The Cox proportional hazards model was employed to examine the interaction between different variables and PFS and OS.Analysis of the association between each component and DCR using logistic regression.The Fisher exact probability approach or the chi-square test were used to compare count data between groups.P-values were two-sided,with univariate analysis P <0.15 was considered as statistically significant,while the rest were considered as P <0.05.Results:1.Study endpoint: Primary study endpoint: median PFS 9.06 months(95%CI:7.046-11.074)and median OS 23.65 months(95%CI:16.968-30.334).Secondary study endpoints: DCR was 76% and ORR was 18%.2.PFS univariate and multivariate analysis: Log-Rank univariate analysis showed that PFS was related to the number of medication lines(P=0.007),ECOG score(P=0.033),and bone metastasis(P=0.027).Multivariate COX regression analysis of P<0.15 and factors considered clinically related to PFS in univariate analysis showed that the ECOG score of 0(HR=0.355,P=0.031),no bone metastasis(HR=3.919,P=0.036)and first-line treatment(HR=2.322,P=0.008)had a higher proportion of exposure in patients with prolonged PFS compared to control factors.Can be considered as a dominant factor for prolonging the PFS.3.OS univariate and multivariate analysis: Log-Rank univariate analysis showed that OS was related to related surgical history(P=0.012)and bone metastasis(P=0.007).Multivariate COX regression of P<0.15 and factors considered clinically related to OS in the univariate analysis showed that patients without bone metastases(P=0.039,HR=4.151)had a lower risk of death.After correction for other related factors,it still showed obvious positive correlation with OS extension and could be considered as the dominant factor for OS extension,and the difference was statistically significant.4.DCR univariate and multivariate analysis: univariate Logistic regression analysis showed: smoking history(OR: 3.333,95%CI 0.779-14.261),combination chemotherapy(OR: 3.000,95%CI 0.701-12.830),which may be the dominant factor for disease control.Multivariate Logistic regression analysis of P<0.15 and factors clinically related to DCR were included in the univariate analysis showed that the proportion of smoking history before medication(OR:5.268,P=0.049)was significantly increased in patients with disease control,which could be considered as the dominant factor of disease control,and the difference was statistically significant.5.Of the 50 patients,the overall rate of adverse events was 84.0%(42/50),most are grades 1-2,the incidence rate was 76.0%(38/50),Grade 3-4 incidence was 26.0%(13/50);The most common(10%)event of patients followed up was myelosuppression(15/50,30.0%),abnormal liver function(14/50,28.0%),fatigue(8/50,16.0%),fever(8/50,16.0%),nausea and vomiting(7/50,14.0%),Rash(7/50,14.0%),Diarrhea(6/50,12.0%),Oral Mucositis(6/50,12.0%).Eight patients stopped medication due to adverse reactions,all of which were within control,and no patient died due to adverse reactions.Depending on whether combination chemotherapy was used,patients were split into groups receiving immune drugs alone and those receiving combination chemotherapy.Among them,the incidence of total adverse events(P=0.006)and the incidence of grade 1-2(P=0.004)in combination chemotherapy group were significantly higher than that of immune single agent group,and the difference was statistically significant.Except for fatigue,patients receiving combination chemotherapy frequently experienced myelosuppression,abnormal liver function,and fever.The incidence of myelosuppression was also significantly higher in the combination chemotherapy group compared to the immune single group(P<0.001)among the top four adverse events with the highest incidence.The connection between adverse events and PFS and OS was examined using the Log-Rank test,although the results were not statistically significant(P≥0.05).Conclusions:1.Immune checkpoint inhibitors are effective enough in treating patients with locally advanced and metastatic UC in real world.2.ECOG score and premedication smoking history may help clinical screening of dominant populations who benefit from immunotherapy.3.Patients with second-line and third-line immunotherapy,and patients with existing bone metastases before immunotherapy may have poor benefit from it.4.Most of the adverse reactions events in real world locally advanced and metastatic UC patients are grade 1-2,and grade 3-4 adverse reactions are mostly within the controllable range.5.Compared with combination chemotherapy,the overall incidence of adverse effects with immune monotherapy was significantly reduced.