Research Progress And Single-centerpreliminary Efficacy Analysis Of Targeted Drug Combined With Immune Checkpoint Inhibitors In The Treatment Of Advanced Renal Cell Carcinoma

Background:incidence rate of RCC is about 2%to 3%of adult malignant tumors.It is the third only to prostate cancer and bladder cance in urinary system.But RCC has the highest mortality rate in urinary system.Because the early symptoms of RCC are hidden,30%of patients have extrarenal metastasis when making a definite diagnosis.Even after radical nephrectomy,30%of patients still have recurrence or distant metastasis.Once metastasis occurs,the 5-year survival rate of patients is only 12%.Effects of traditional radiotherapy,chemotherapy and interferon-α,etc on mRCC are not obvious.The current median survival is only 18 months.Since Sorafenib was approved by the U.S.FDA for the treatment of mRCC in 2005,the treatment of mRCC has entered an era dominated by targeted therapy.However,almost all patients will be resistant to targeted therapy.Therefore,it is necessary and urgent to find new treatment protocols in order to continuously improve the prognosis of patients with mRCC.In recent years,with the deepening of the research on the regulatory mechanism of the immune system and the emergence of ICI,the biotherapy with tumor immunotherapy as the core has developed rapidly.In 2015,FDA approves Nivolumab,an anti PD-1 was used for the second-line treatment of mRCC,which marked the beginning of immunotherapy for mRCC.NCCN guidelines recommend that combination therapy be used for the first treatment of low,medium and high-risk people by IMDC,but in 2020,The ASCO conference announced that the long-term subgroup analysis results of KEYNOTE 426 study showed that low-risk patients could not benefit from combination therapy.Based on this,in the CSCO guidelines for RCC published in 2020,the class I recommendations for low-risk patients are still targeted therapy,while the class I recommendations for medium and high-risk patients with mRCC are combined immunotherapy.At present,,ICI drugs such as Tirelizumab have been approved for the treatment of urothelial cancer in our country,but have not been approved for the treatment of RCC.And there is still a lack of real-world research on targeted drug combined with ICI in the treatment of mRCC.Therefore,this paper retrieves related literature about this hot research,collects and summarizes the information of patients treated with targeted duug combined ICI in Shandong Provincial Hospital in recent 2 years,preliminarily evaluates its efficacy and safety,for enriching the clinical workers’cognition of the treatment scheme in the real world.Objective:to retrieve and summarize the research progress of targeted drug combined ICI in the treatment of mRCC at home and abroad,and preliminarily evaluate its effectiveness and safety bansed on our hospital single-center real world clinical cases.Materials and methods:17 patients with mRCC treated by targeted drugs combined with ICI in Shandong provincial hospital from October 2019 to December 2021 were selected for this research objects.The efficacy of combined medication shall be evaluated at least once every two cycles,and the treatment effect and related adverse reactions shall be analyzed.Results:the median follow-up time was 7.0(1.2～12.4)months,17 cases could all evaluate the curative effect,including 13 cases of PR,3 cases of SD and 1 case of PD.The ORR was 76.5%(13/17),the DCR was 94.1%(16/17).Due to the short follow-up time,this study did not reach the mOS and mPFS.The incidence of adverse reactions in all patients was 94.1%(16/17),and the incidence of grade 3/4 adverse reactions was 17.6%(3/17),and there was no grade 5 death.The common adverse reactions included gastrointestinal reactions(9/17),skin reactions(8/17)and hypertension(6/17).There were 2 patients with hematotoxicity in this group,2 patients with gingivitis,1 patient with subclinical myocardial injury,1 patient with immune hepatitis,and 1 patient with pancreatitis.There were no patients with renal toxicity,immune pneumonia,osteoarthritis and muscle toxicity and other rare toxicity in this group.Conclusion:The combination of anti vascular targeted drugs and immune checkpoint PD-1/PD-L1 inhibitors has significant clinical efficacy in the treatment of mRCC.The incidence of severe adverse reactions is low and controllable.It can be used as the first-line treatment or the back-line choice for patients with initial multitarget tyrosine hormone inhibitor targeted treatment failure.