Efficacy And Safety Analysis Of Sintilimab Combined With Chemotherapy In The First-line Treatment Of Advanced Squamous Non-small Cell Lung Cancer

BackgroundAccording to different biological characteristics and treatment methods,lung cancer can be divided into two categories: small cell lung cancer(SCLC)and non-small cell lung cancer(NSCLC).Squamous NSCLC is a unique histological subtype of NSCLC,accounting for about 30%.Due to its unique epidemiological,histopathological and molecular characteristics,treatment is challenging,including older age and advanced diagnosis at the time of diagnosis.,Easy to form cavities and compared with non-squamous NSCLC,the incidence of co-morbidities such as chronic obstructive pulmonary disease and heart disease is higher.Since it is usually located in the center and occurs in the proximal bronchi,it is more likely to invade large blood vessels and have a high risk of hemoptysis.In addition,sensitive driver gene mutations for which targeted therapy has been approved are rare in squamous NSCLC.At present,its first-line treatment is still platinum-containing double-drug chemotherapy with taxanes or gemcitabine combined with platinum,with a poor prognosis.The treatment of tumor immune checkpoint inhibitors has been a hot spot for research and development in recent years,and has continued to obtain huge breakthroughs,mainly including cytotoxic T lymphocyte antigen 4(CTLA-4)and programmed death receptor 1/programmed death ligand 1(PD1/PD-L1),of which PD-1/PD-L1 is the most studied.Previously,a number of phase 3 studies have compared the efficacy and safety of PD-1/PD-L1 inhibitor combined with chemotherapy and chemotherapy alone in patients with advanced squamous NSCLC,showing the advantages of combined therapy.Sintilimab is a recombinant fully human Ig G4 PD-1 monoclonal antibody independently developed in my country.It has been approved for the clinical treatment of relapsed or refractory classic Hodgkin’s lymphoma after second-line chemotherapy.At present,Sintilimab has been used as a single agent for preoperative neoadjuvant treatment of NSCLC and early clinical studies of combined chemotherapy in the first-line treatment of NSCLC have confirmed that it has strong anti-tumor activity and good tolerability.ObjectiveTo evaluate the efficacy and safety of Sintilimab combined with chemotherapy in the first-line treatment of advanced squamous NSCLC,and to provide patients with better treatment options.MethodsStarting from December 2018,according to the inclusion criteria and exclusion criteria,60 patients with advanced squamous NSCLC will be screened and divided into observation group and control group with 30 cases each.The control group will be given gemcitabine,1g/㎡,intravenous drip,the first 1,8 days,cisplatin,75mg/㎡,intravenous drip,the first day,Q3 W.The observation group was added with Sintilizumab 200 mg on the basis of the control group,intravenous drip,on the first day,Q3 W,after 4-6 cycles of continuous treatment,followed by Sintilizumab or placebo for maintenance treatment until Disease progression,death or intolerable toxicity occurs.The main observational endpoint is progression free survival(PFS).The PFS,objective response rate(QRR),disease control rate(DCR),tumor marker levels,quality of life,and adverse events were compared between the two groups to evaluate Sintilizumab combined with chemotherapy in the treatment of advanced squamous NSCLC to evaluate the efficacy and safety.Results1.The median PFS of the observation group was 7.8 months(95%CI:6.514-9.153),and the control group was 5.6 months(95%CI: 4.822-6.378)([2]=9.002,P=0.003).After 4 cycles of treatment,the ORR of the observation group was higher than that of the control group(50% vs 26.67%,P<0.05),and the DCR(86.67% vs77.67%)of the two groups were similar,and the difference was not statistically significant.2.The levels of squamous cell carcinoma antigen,carcinoembryonic antigen,and cytokeratin 19 fragment before treatment in the observation group and the control group were not different(P>0.05),and after 4 cycles of treatment,they were all lower than before treatment(P<0.05),and The reduction level of the observation group was significantly higher than that of the control group(P<0.05).3.There was no difference in the quality of life between the observation group and the control group before treatment(P>0.05).After 4 cycles of treatment,the scores of functional areas and overall health status of the two groups decreased,and the scores of main symptoms and specific items increased,with significant differences(P<0.05)The functional areas and overall health status of the observation group after treatment were higher than those of the control group,and the main symptoms and specific items were lower than those of the control group,which was statistically significant(P<0.05).4.There were no deaths due to adverse reactions during the treatment.The most common adverse reactions are anemia(76.67% vs 73.33%),neutropenia(70% vs63.33%),thrombocytopenia(66.67% vs 63.33%),but most of them are grade 1-2,The difference between the two groups was not statistically significant.Among the immune-related adverse reactions(Immune-related Aes,ir AEs),the incidence of hypothyroidism,skin rash,diarrhea,arrhythmia,and hypoproteinemia in the observation group was higher than that in the control group,most of which were grade 1-2,and were relieved after symptomatic treatment.In general,toxicity is acceptable,bone marrow suppression is a common adverse reaction,and non-hematological toxicity is generally mild.ConclusionSintilimab combined with chemotherapy in the first-line treatment of advanced squamous NSCLC can prolong PFS,down-regulate the level of tumor markers,improve the quality of life,tolerate toxicity,and have good safety.