Comparison Of Efficacy And Safety Of Regorafenib With Or Without PD-1 Inhibitors In The Second-line Treatment Of Advanced Hepatocellular Carcinoma

Background:Regorafenib is the first oral targeted drug as a second-line agent in patients with advanced hepatocellular carcinoma(HCC)who progressed on sorafenib treatment.Recently,several studies demonstrated that the combination of regorafenib and PD-1inhibitors showed a synergistic effect.Objective:Our study aimed to evaluate the efficacy of regorafenib with PD-1 inhibitors(RP)and regorafenib alone(R)as second-line treatment for advanced HCC.Methods:From October 2018 to January 2022,our retrospective study evaluated advanced HCC patients who received regorafenib with PD-1 inhibitors or regorafenib alone as a second-line treatment at the Second Affiliated Hospital of Nanchang University.The efficacy was evaluated based on m RECIST and RECIST1.1,and the safety and AE was evaluated by CTCAE 5.0.Progression-free survival(PFS)and overall survival(OS)was calculated by the Kaplan-Meier method,and prognostic factors were analyzed by the Cox regression model.Results:1.78 patients were included in this study and were divided into two groups according to the criteria: RP group(n = 48)and R group(n = 30).The objective remission rate(ORR)of RP group was 18.8%(m RECIST)and 12.5%(RECIST1.1),the disease control rate(DCR)was 66.7%(m RECIST)and64.5%(RECIST1.1),the ORR of R group was 10.0%(m RECIST)and 6.7%(RECIST1.1),DCR was 43.3%(m RECIST and RECIST1.1).2.The median PFS and median OS of RP group patients were 5.9 months and 12.9months,while the median PFS and median OS of R group patients were 3.0months and 10.3months respectively.3.In the subgroup analysis of OS,patients with AFP ≥ 400ng/m L,BCLCC and extrahepatic metastasis may benefit from RP,while in the subgroup analysis of PFS,patients with BCLCC stage,AFP ≥ 400ng/m L,extrahepatic metastasis,ALBI ≥-2.60 and previous sorafenib first-line treatment may benefit from RP.4.In this study,the incidence of grade 3/4 adverse reactions in patients with RP group was 22.9%.In the R group,the incidence of grade 3/4 adverse reactions was 23.3%.5.The results of COX univariate and multivariate analysis showed that regorafenib monotherapy was an independent risk factor for PFS and OS.Conclusion:In the second-line therapy of advanced HCC,compared to regorafenib alone,the combination of regorafenib and PD-1 inhibitors showed promising efficacy and tolerable drug toxicity.