Efficacy And Safety Of Camrelizumab Combined With Apatinib As Adjuvant Therapy For Postoperative Patients With Advanced Oral Squamous Cell Carcinoma

Background and purposeOral squamous cell carcinoma(OSCC)is a common malignant tumor,which usually occurs in the mucosa of lip and cheek,anterior 2/3 of the tongue,the base of mouth,posterior molar area,maxillary and mandibular gingiva and hard palate.OSCC has a high morbidity and disability rate which shows a rising trend year by year,seriously threatening the health and quality of life in patients.At the same time,more and more studies have found that the age of patients are gradually younger.Patients with early OSCC can get better prognoses with single treatment,but more than half of patients are diagnosed with advanced stages,and their overall 5-year survival rate is less than 40%.Over the years,traditional treatment modes such as surgery combined with radiotherapy and chemotherapy have achieved some clinical effects in controlling the recurrence and metastasis of tumor,but we need to explore safe and effective treatment methods in advanced OSCC because of the limitations of drug efficacy and the serious adverse events of patients after medication.In recent years,scholars have paid more attention to the role of angiogenesis in the development of tumorigenesis.Vascular endothelial growth factor(VEGF)and vascular endothelial growth factor receptor(VEGFR)are important regulatory molecules of signaling pathways in angiogenesis.Anti-angiogenesis targeted drugs have shown superior anti-tumor efficacy than traditional therapy in multiple tumor species,and Apatinib,which is one of the most representative drugs,can specifically bind to VEGFR-2 to block vascular growth in tumor tissue.However,there are deficiencies including drug resistance and explosive progression of tumor after antiangiogenesis targeted drug discontinuance.At the same time,tumor progression is also closely related with the changes of immune status,and it further promote the formation of immunosuppressive tumor microenvironment.Patients of OSCC often occur immune evasion,so the immunotherapy of targeting programmed cell death 1(PD-1)and programmed cell death ligand 1(PD-L1)can achieve anti-tumor effects by restoring the activity and function of immune cells.As a PD-1 inhibitor,Camrelizumab can significantly improve the survival rate of patients with advanced lung cancer,esophageal squamous cell carcinoma and liver cancer,but the immunosuppressive tumor microenvironment restricts the efficacy of immunotherapy.The combined application of Camrelizumab and Apatinib,which makes them participate in the adjustment of immune status together,can compensate for the insufficient efficacy of single agent to show the synergetic effect.The purpose of this study was to observe and research the efficacy and safety of this combined therapy in postoperative patients with advanced OSCC,and provide evidence support for clinical treatment.MethodsRetrospectively analysed the advanced OSCC patients who were treated in the Department of Oral and Maxillofacial Surgery of the First Affiliated Hospital of Zhengzhou University from 2019.2 to 2022.2,and the total number of patients was 56.According to the different methods of postoperative adjuvant treatment,the patients were divided into experimental group and control group,and the number of patients in the two groups was 29 and 27 respectively.The experimental group was treated with Camrelizumab combined with Apatinib,and the control group was treated with traditional chemotherapy combined with Apatinib.The local control rate of primary tumor,distant metastasis,the control rate of cervical lymph node,disease free survival(DFS)and the incidence of adverse events in each group were followed up and observed to evaluate the efficacy and safety of Camrelizumab combined with Apatinib as adjuvant treatment for the postoperative patients of advanced OSCC.Results1.The follow-up time of patients in the experimental group was 9-35 months,and the median follow-up time was 13.0 months.The follow-up time of patients in the control group was 5-16 months,and the median follow-up time was 9.0 months.2.The local control rate of primary tumor in the experimental group and control group was 48.3%(n=14)and 48.1%(n=13)respectively.No distant metastasis occurred in either group of patients.3.The control rate of cervical lymph node in the experimental group and control group was 89.7%(n=26)and 66.7%(n=18)respectively,and the difference was significant(P=0.036).4.In the analysis of the total population,the median DFS in the experimental group and control group was 14.0 months(95%CI:12.4-15.6)and 11.0 months(95%CI:8.8-13.2)respectively,and the difference was significant(χ2=8.743,P=0.003).After the subgroup analysis of the patients in two groups,it was found that the median DFS in the experimental group was significantly higher than the median DFS in the control group in the subgroup of patients with N-,clinical stageⅢ,female and pathological grade with high differentiation(P<0.05).5.The incidence of leukopenia in the experimental group decreased significantly compared with the control group,which was 13.8%(n=4)and 40.7%(n=11)(P=0.023)respectively.The incidence of gastrointestinal symptoms such as nausea and vomiting in the experimental group was also significantly lower than the incidence of gastrointestinal symptoms in the control group(P=0.034),and the grades of aforementioned adverse events in the experimental group were all 1-2.There was no significant difference in the incidence of the other adverse events between two groups(P>0.05).ConclusionsCamrelizumab combined with Apatinib has good tumor control and survival benefits as adjuvant therapy for the postoperative patients of advanced OSCC,and the safety is controllable.