Efficacy And Safety Analysis Of Sintilimab Combined With Chemotherapy In The Treatment Of Advanced Non-Small-Cell Lung Cancer

Objective:In this study,132 patients with advanced non-small-cell lung cancer（NSCLC）treated in the First Hospital of Jilin University were retrospectively analyzed to evaluate the efficacy and safety of sintilimab combined with chemotherapy in the real world.The predictors that may affect the prognosis were also explored to provide reference for the application of sintilimab in the real world.Methods:The clinical data of 132 advanced NSCLC patients who received sintilimab combined with chemotherapy in the First Hospital of Jilin University from January 1,2016 to September 31,2021 were collected by consulting the electronic medical record system.Clinical data mainly included gender,age at diagnosis,smoking history,pathological type,clinical stage,pulmonary lesions and metastasis,treatment plan.Neutrophil count,platelet count,lymphocyte count and monocyte count in peripheral blood 1 week before the first treatment with sintilimab combined with chemotherapy were also collected.Neutrophil to lymphocyte ratio（NLR）,platelet to lymphocyte ratio（PLR）,lymphocyte to monocyte ratio（LMR）and other indicators were calculated.Response Evaluation Criteria In Solid Tumors（RECIST）version 1.1 was used to evaluate the efficacy of the patients.Safety was evaluated according to the Common Terminology Criteria for Adverse Events（CTCAE）version 5.0.The effects of clinical features and inflammatory indicators on progression free survival（PFS）and overall survival（OS）were analyzed,and independent risk factors affecting long-term prognosis of patients were screened.Results:1.All 132 patients included in the study completed more than 2 cycles of sintilimab combined with platinum-containing two-drug chemotherapy.Among 132 patients,61 achieved partial remission（PR）,24 achieved stable disease（SD）,47 achieved progression of disease（PD）.The disease control rate（DCR）was 64.4% and the objective response rate（ORR）was 46.2%.The overall median PFS was 9.20 months and the median OS was 18.43 months.As of December 1,2021,81 patients（61.4%）had experienced disease progression and 50 patients（37.9%）had died.2.The relationship between ORR and clinical characteristics and inflammatory indicators was evaluated by Chi-square test.The results showed that male patients,patients with squamous cell carcinoma,first-line sintilimab combined with chemotherapy,earlier tumor stage,no pleural metastasis,NLR≤2.7,PLR≤137.5,and LMR > 2.9 had better response to sintilimab combined with chemotherapy（P < 0.05）.3.Univariate analysis showed that patients with earlier clinical stage,first-line treatment,combined radiotherapy,no liver metastasis or brain metastasis had a later time of disease progression and significantly prolonged PFS（P < 0.05）.Patients with combined radiotherapy,early tumor stage,no liver or pleural metastasis,NLR≤2.7,PLR≤137.5 and LMR > 2.9 before treatment had longer overall survival and better long-term prognosis（P < 0.05）.4.Multivariate analysis showed that patients with late N stage,liver metastasis,and second-line chemotherapy or above treated with sintilimab had earlier disease progression and shorter PFS.Patients with combined radiotherapy,early T stage and N stage and low PLR level had better long-term prognosis and longer OS.5.Safety analysis: among the 132 patients included in the study,the overall incidence of adverse events was 97.7%（129/132）,and the incidence of grade 3 and above adverse events was 50.0%（66/132）.Common adverse events included leukopenia（79.5%）,anemia（59.8%）,fatigue（34.1%）,thyroid dysfunction（31.8%）,thrombocytopenia（26.5%）,nausea and vomiting（19.7%）,limb numbness（16.7%）,abnormal liver function（15.2%）,and rash（13.6%）.Grade 3 and above adverse events mainly included leukopenia（35.6%）,anemia（11.4%）,checkpoint inhibitor-related pneumonia（CIP）（5.3%）,hepatic dysfunction（3.0%）,thrombocytopenia（3.0%）.Treatment was discontinued in 15 patients（11.4%）due to adverse events,including 1case of fatigue and limb numbness,1 case of hypopigmentation,3 cases of checkpoint inhibitor-associated myocarditis,7 cases of CIP,2 cases of nausea and vomiting,and 1case of checkpoint inhibitor-associated encephalitis.The toxicity of sintilimab combined with chemotherapy in the real world was controllable,and no deaths caused by adverse events occurred.Conclusions:1.In the real world,sintilimab combined with chemotherapy has a positive efficacy and is well tolerated in patients with advanced NSCLC,a short course of combined therapy may also bring long-term survival benefits.2.For patients who start sintilimab combined with chemotherapy for first line treatment after diagnosis,with early T stage and N stage and no liver metastasis,disease progression occur later.Patients with late T stage at diagnosis,PLR>137.5 before treatment and no combined radiotherapy have shorter OS and poor long-term prognosis.3.In the real world,the incidence of immune-related adverse reactions,such as CIP,immune checkpoint inhibitor-associated myocarditis and immune checkpoint inhibitor-associated encephalitis are low,but most of them are grade 3 or above adverse events,which should be recognized and monitored throughout the clinical process to strive for early diagnosis and treatment.