| According to the latest data of GLOBOCAN in 2021,there were about 2.2 million new cases of lung cancer in 2020,accounting for 11.4% of all new cases of cancer in the world,and about 1.8 million deaths,accounting for 18.0% of the total cancer deaths.It has ranked first among all tumors.In China,the incidence rate of lung cancer ranks first.According to statistics,the number of deaths has exceeded 700 thousand in 2020.Lung cancer has become a serious disease threatening human health.It is urgent to treat this disease.About 80% of all lung cancer cases are non-small cell lung cancer(NSCLC),and most patients are in advanced stage when they are found,and their 5-year survival rate is very low.Therefore,there is an urgent need to find an effective method to treat NSCLC.At present,in the early clinical treatment of NSCLC,the main methods are surgery,radiotherapy and chemotherapy.Surgery is mainly used for early and mid-term localized lung cancer.Although radiotherapy has a certain effect on some patients with advanced NSCLC,there are often serious complications,such as radiation esophagitis,radiation pneumonia and so on;In addition,as radiotherapy is a local treatment,it is often used in combination with chemotherapy clinically.About 40-50% of NSCLC patients treated with chemotherapy can be relieved,but it can only improve the patient’s condition but not cured.Moreover,chemotherapy is systemic treatment,which mainly has two limitations,tumor drug resistance and adverse drug reactions.Therefore,people began to look for more suitable treatment.With the discovery of immune checkpoint molecules,such as programmed death receptor 1(PD-1)and programmed death ligand 1(PD-L1),these molecules can play an important role in tumorigenesis and development by inhibiting the function of immune cells.Therefore,monoclonal antibodies against immune checkpoints have been developed to treat a variety of tumor patients,including NSCLC.However,the application effects of PD-1 / PD-L1 in lung cancer patients are different,and some patients have poor response or serious side effects.Therefore,people try to adopt combined treatment methods,such as anti-PD-1 combined radiotherapy,anti-PD-1combined chemotherapy,etc,However,the efficacy of this combination therapy is still controversial.Therefore,in order to understand the role and efficacy of different antibodies PD-1 monoclonal antibodies combined with chemotherapy in the treatment of NSCLC,two kinds of anti-pd1 antibodies(i.e.pabolizumab or carrelizumab)were used to treat patients with advanced NSCLC.At the same time,the simple chemotherapy group was set as the control.By comparing the main efficacy endpoint orr between different groups,Secondary end points included objective response rate(ORR),median progression-free survial(m PFS),duration of response,(DOR),overall survivial(OS),as well as the occurrence of adverse events.The efficacy of this combination therapy was evaluated to provide experimental basis for guiding the clinical selection of reasonable,safe and effective regimen for the treatment of NSCLC patients.The research is mainly divided into the following two aspects:Ⅰ.Efficacy of pabolizumab combined with chemotherapy in the treatment of advanced non-small cell lung cancer1.General conditions of patients in the two groupsFirstly,in order to make sure that the general data of the two groups are comparable,among the 60 patients included,there were 19 males and 11 females in the simple chemotherapy group;The age ranged from 18 to 80 years old,with an average of(61.28± 11.17)years old.There were 20 males and 10 females in the combined group;The age ranged from 18 to 80 years old,with an average of(60.89 ± 13.23)years old.Comparing the general data of the two groups,there was no significant difference in gender and age between the two groups(P > 0.05).In addition,in order to exclude the influence of different lung cancer types on the treatment effect of the two groups,we compared the distribution of pathological types between the two groups.Among the 30 patients treated with the pabolizumab combined chemotherapy,including 19 cases of adenocarcinoma,4 cases of squamous cell carcinoma and 7 cases of other types(including large cell carcinoma and sarcomatoid carcinoma).n the 30 cases of simple chemotherapy group,there were 15 cases of adenocarcinoma,9 cases of squamous cell carcinoma and 6 cases of other types.Through statistical analysis,except that adenocarcinoma was higher in the combined group than in the chemotherapy group(P >0.05),there was no difference in the distribution of other pathological types and the total types between the two groups(P < 0.05).The results show that on the whole,the pathological types of lung cancer in this study will not be the influencing factors for the comparison of the two treatment effects.2.Comparison of curative effects between the two groups(1)Overall evaluation of the efficacy of the two groups after treatmentIn order to judge the difference of the therapeutic effects of the two treatment methods,the complete response(CR),partial response(PR),progressive disease(PD),stable disease(SD)and total effective rate of the two groups were compared.The results showed that the PR and SD of the combined pabolizumab group were higher than those of the simple chemotherapy group,and the total effective rate was also significantly higher than that of the simple chemotherapy group(P < 0.05).(2)Comparison of PFS between the two groupsIn order to comprehensively evaluate the therapeutic effects of the two treatment methods,the median progression free survival(m PFS)of the two groups were further compared.The results showed that the m PFS of the combined group was 10.2 months.Compared with the chemotherapy group,which was 3.3 months longer than that of the chemotherapy group(6.9 months).The difference between the two groups was statistically significant(P < 0.05).3.Comparison of two groups of OS,ORR and DORIn order to further evaluate the therapeutic effect of pabolizumab combined with chemotherapy,the differences of OS,ORR and DOR between the two groups were compared.The results showed that compared with the simple chemotherapy group,pabolizumab combined with chemotherapy improved OS [hazard ratio(HR)0.63;95%confidence interval(CI)0.50 ～ 0.79].In the pabolizumab combined chemotherapy group,18 patients completed 2 years of treatment,and their ORR was 79.8%(95% CI 61.7% ～ 98.4%),and the 2-year overall survival rate was 87%.In addition,for patients with PD-L1 negative tumors,the ORR(67%;95% CI 56.3% ～ 67.9%)of pabolizumab combined with chemotherapy group was higher than that of chemotherapy group alone(33.7%;95% CI 31.2% ～ 37.9%).The difference was statistically significant(P< 0.05).The median DOR was 11.7months in the combination group,and 8.8 months in chemotherapy alone group,respectively.There was no significant difference between the two groups(P> 0.05).The above results show that the combined chemotherapy of pabolizumab can improve the OS and ORR of patients compared with the simple chemotherapy group,and has a better therapeutic effect.4.Comparison of adverse events between the two groupsTo observe the incidence of adverse drug reactions in two groups of the patients in the two groups,the incidence rate of several common adverse events in the two groups was analyzed statistically.The results showed that the incidence of adverse events(AE)in the combination group and chemotherapy group were 67% and 71.5%respectively,of which the incidence of grade 3-5 AE was 57.4% and 63.7% respectively,and the incidence of immune-mediated AE and infusion reaction were 14.5% and 13.1%respectively.Statistical analysis showed that there was no significant difference in the incidence of adverse events between the two groups(P> 0.05).It is suggested that there is no difference in the common adverse events caused by combined chemotherapy with pabolizumab and simple chemotherapy,that is,the combination of pabolizumab can not particularly improve the side effects caused by chemotherapy.Ⅱ.Effect of carrelizumab combined with chemotherapy in the treatment of advanced non-small cell lung cancer1.General conditions of patients in the two groupsFirstly,in order to make sure that the general data of the two groups are comparable,we counted the basic situation of patients in the combined chemotherapy group and the simple chemotherapy group.There were 30 cases in the simple chemotherapy group,including 21 males and 9 females.The age ranged from 18 to 80 years old,with an average of(59.37 ± 10.23)years old.There were 30 cases in the combined group,18 males and 12 females.The age ranged from 18 to 80 years old,with an average of(63.57 ± 9.81)years old.The results showed that there was no significant difference between the two groups(P> 0.05),indicating that the two groups were comparable.In order to exclude the influence of different lung cancer types on the treatment effect of the two groups,we compared the distribution of pathological types between the two groups.Among the 30 cases included in the carrelizumab combined chemotherapy group,there were 16 cases of adenocarcinoma,9 cases of squamous cell carcinoma and 5 cases of others.Among the 30 cases in the simple chemotherapy group,there were 12 cases of adenocarcinoma,16 cases of squamous cell carcinoma and the other 2 cases.There was no significant difference in the distribution of most patients(adenocarcinoma and squamous cell carcinoma)and the total types between the two groups(P> 0.05),and other types in the combined group were slightly higher than those in the chemotherapy group(P< 0.05),suggesting that the main pathological types of lung cancer in this study will not be the influencing factors for the comparison of the two treatment effects.2.Comparison of curative effects between the two groups(1)The curative effect was evaluated after two cycles of treatmentIn order to judge the difference between the two treatment methods,the total effective rates of the two groups were compared.The results showed that the combined group(83.33%)was higher than the control group(56.67%)(P< 0.05);The rate of CR patients in both groups was 0;The SD of carilizumab combined group was 15 patients.It was higher than that of simple chemotherapy group,which 6 patients is belong to SD.(2)Comparison of m PFS between the two groupsIn order to comprehensively evaluate the therapeutic effects of the two treatment methods,the median progression free survival rate(m PFS)of the two groups was further compared.The results showed that m PFS in the carrelizumab combined group was prolonged by 5.3 months compared with that in the simple chemotherapy group(17.20 months vs 11.9 months).The difference was statistically significant(P< 0.05).3.Comparison of adverse events between the two groupsIn order to evaluate the difference of adverse events between the two treatment methods,the results showed that the total incidence of the combined group was 67%and that of the simple chemotherapy group was 47%.The most common adverse events in the combined chemotherapy group were skin capillary hyperplasia(6/30)and gastrointestinal reaction(6/30).In the simple chemotherapy group,the most common adverse events were gastrointestinal reaction(4/30)and capillary hyperplasia(3/30),followed by nervous system injury(2/30),hypothyroidism and fever.Compared with the control group,RCHs was a specific adverse event of carrelizumab,and the difference was statistically significant(P< 0.001).There was no significant difference in the incidence of grade 3-4 adverse events between the two groups.In addition,there were no treatment-related fatal events in both groups.Conclusion:1.one Compared with the control group,pabolizumab combined with chemotherapy improved the OS and m PFS of patients and prolonged them by 3.3months.In patients with PD-L1 negative tumors,ORR in the combined treatment group was higher than that in the control group.There was no difference in the total incidence of adverse events between the two groups.2.Compared with the control group,the total effective rate and PR of carelizumab combined chemotherapy were higher;m PFS was prolonged by 5.3 months;There was no difference in the total incidence of adverse events between the two groups,but RCHS was a specific adverse event of carrelizumab. |
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