Efficacy And Prognostic Factors Analysis Of Camrelizumab Combined With Chemotherapy For Advanced Esophageal Squamous Cell Carcinoma

Background and ObjectiveEsophageal cancer is a common gastrointestinal malignancy in the domestic and foreign,which seriously affects the development of global public health.Esophageal cancer has obvious regional differences,mostly concentrated in East Asia and Southeast Africa.Squamous cell carcinoma of esophagus is the most common pathologic subtype of esophageal cancer in China.Because the early symptoms of esophageal squamous cell carcinoma are not typical clinically,the vast majority of patients have advanced or spread to other sites by the time they are initially diagnosed.Although the comprehensive diagnosis and treatment technology of esophageal squamous cell carcinoma has made progress,the overall therapeutic effect is still not ideal,and the 5-year survival rate is only 15%-25%.Accordingly,it is absolutely important to optimize the existing therapeutic regimens and explore new treatment models for increasing the survival rate of patients.In recent years,with the emergence of immune checkpoint inhibitors,multiple malignant tumors such as malignant melanoma,Hodgkin’s lymphoma,non-small cell lung cancer,hepatocellular carcinoma and renal cell carcinoma have entered the era of immunotherapy and achieved significant results.As an important part of immunotherapy,anti PD-1/PD-L1 antibody has become a research hotspot in the field of advanced esophageal squamous cell carcinoma.With the release of the results of phase III clinical study Keynote-181,the survival benefit of anti PD-1/PD-L1 antibody in immunotherapy of esophageal cancer was confirmed for the first time.Camrelizumab is a high-affinity,fully humanised,IgG4κ PD-1 monoclonal antibody.For advanced esophageal squamous cell carcinoma,Camrelizumab has been approved by National Medical Products Administration(NMPA)for the treatment of locally advanced or metastatic esophageal squamous cell carcinoma which progresses following previous first-line chemotherapy or was intolerant to previous first-line chemotherapy.Nevertheless,the efficacy of camrelizumab combined with chemotherapy in patients with advanced esophageal squamous cell carcinoma is still unclear.This study retrospectively analyzed the patients with advanced esophageal squamous cell carcinoma treated in our hospital to explore the clinical efficacy,adverse reactions and prognostic factors of camrelizumab combined with chemotherapy in the second-line therapy of advanced esophageal squamous cell carcinoma.MethodsRetrospective analysis of clinical materials of 115 patients with advanced squamous cell carcinoma of esophagus,from December 2018 to May 2020,admitted to oncology department of the First Affiliated Hospital of Zhengzhou University.Depending on the different therapeutic regimens,the patients were divided into observation group and control group.56 patients in the control group received standard second-line chemotherapy,while 59 patients in the observation group received camrelizumab combined with standard second-line chemotherapy.The corresponding statistical methods were used to compare the progression free survival,disease control rate,objective response rate,adverse reactions and safety profile of two groups of patients.According to the clinical data and follow-up of patients,Kaplan-Meier analysis and COX multivariate regression model were used to analyze the prognostic factors of advanced esophageal squamous cell carcinoma treated with second-line treatment,and the correlation between the expression of PD-1/PD-L1 and the efficacy of camrelizumab combined with standard second-line chemotherapy in the treatment of advanced esophageal squamous cell carcinoma.Results1.Short-term efficacy:The disease control rate was 74.6%in the observation group and 69.7%in the control group,and the objective response rate was 22.0%and 17.9%respectively.The disease control rate and objective remission rate of the observation group were slightly higher than those of the control group,but the differences were not statistically significant(P>0.05).2.Survival analysis:Median progression-free survival of patients in the observation group(5.6months,95%CI 4.14～7.06months)was prolonged obviously than that in the control group(4.2months,95%CI 3.40～5.00months).Compared with the control group,the progression-free survival of patients in the observation group was prolonged(P=0.039),and the difference was statistically significant.3.Adverse reactions:The adverse reactions were mainly grade Ⅰ～Ⅱ.The incidences of nausea and vomiting,neutropenia,thrombocytopenia,loss of appetite,liver and renal dysfunction in the observation group were lower than those in the control group,but the anemia,fatigue,reactive cutaneous capillary endothelial proliferation,fever and thyroid dysfunction were higher than those in the control group,and the difference of nausea and vomiting(χ2=3.869,P=0.049)and neutropenia(χ2=4.530,P=0.033)was statistically significant.4.Prognostic factors:Kaplan-Meier univariate analysis found that degree of differentiation(P=0.020),PD-1/PD-L1 expression(P=0.044),the ECOG score(P=0.051)and therapeutic regimen(P=0.039)were statistically significant in the prognosis of esophageal squamous cell carcinoma(P<0.1).After further multivariate COX regression analysis,degree of differentiation(P=0.029),PD-1/PD-L1 expression(P=0.036)and therapeutic regimen(P=0.033)were prognostic influencing indicators of progression-free survival in advanced ESCC patients treated with second-line treatment.In observation group,the median progression-free survival(6.8months)in patients with high PD-1/PD-L1 expression was significantly higher than that in patients with low PD-1/PD-L1 expression(4.4months),and the difference was statistically significant(χ2=4.430,P=0.035).In the control group,the median progression-free survival was 4.8 months for patients with high PD-1/PD-L1 expression and 3.9 months for patients with low PD-1/PD-L1 expression,and the difference was not statistically significant(χ2=0.716,P=0.398).The expression of PD-1/PD-L1 was correlated with the efficacy of camrelizumab combined with standard second-line chemotherapy in esophageal squamous cell carcinoma.Conclusions1.As the second-line treatment of advanced ESCC patients,camrelizumab combined with chemotherapy shows more advantage in high remission rate,and its efficacy is better than that of single chemotherapy group.Compared with standard chemotherapy,there is no increase in the incidence of adverse events,and the safety is controllable,with considerable survival benefits.2.Degree of differentiation,PD-1/PD-L1 expression and therapeutic regimen are independent prognostic factors affecting progression-free survival in patients with advanced ESCC treated with second-line treatment.3.PD-1/PD-L1 expression can be used to predict the efficacy of camrelizumab combined with chemotherapy in the second-line treatment of advanced esophageal squamous cell carcinoma.