Efficacy And Safety Of Regorafenib Combined With Immune Checkpoint Inhibitors In The Third-line And Beyond Treatment Of Advanced Colorectal Cancer

Background: We aimed to explore the efficacy and safety of regorafenib combined with Toripalimab in the third-line and beyond treatment of advanced colorectal cancer.Methods: We evaluated the outcomes of MSS patients with advanced colorectal cancer who received regorafenib combined with ICIs in the Second Affiliated Hospital of Nanchang University from June 2019 to January 2021.Thirty-three patients took regorafenib 80 mg or 120 mg once daily for 21 days,28 days as a cycle,combined with Toripalimab /Camrelizumab/Sintilimab until disease progression or intolerant to adverse reactions.We used Kaplan-Meier method to estimate the rate of progression-free survival(PFS)and Log rank method to do statistical test of survival curve.Cox regression model was used to analyze the influence of multiple factors on PFS.We evaluated the efficacy every two cycles and observed the incidence of adverse reactions.Results:The evaluation of treatment effect were assessed according to RECIST1.1.Four patients(12.12%)got partial response,twelve patients(36.36%)experienced stable disease,seventeen patients(51.52%)suffered progressive disease.ORR was 12.12% and DCR was 48.48%.m PFS was 113 days(95%CI:0-272.1).In univariate analysis,PFS was significantly shortened in patients who received previous third-line or higher treatment,received bevacizumab,lung metastases,and APC mutations.Multivariable Cox regression analysis showed number of previous chemotherapy lines,excision of primary lesion and KRAS mutations were independent prognostic factors.The most common treatment related adverse reactions were hand-foot syndrome(33.33%),liver dysfunction(27.27),hypothyroidism(24.24%),Fever(24.24%),fatigue(21.21%),leukopenia(15.15%),hypertension(12.12%),platelet count decreased(6.06%),diarrhea(3.03%)and myocarditis(3.03%),one patient stopped treatment as myocarditis.The incidence of grade 3/4adverse reactions was 9.09%.Conclusion: Regorafenib combined with ICIs have a promising effect in the third-line and beyond treatment of advanced colorectal cancer.The treatment related adverse reactions are tolerant in combined therapy.