酪氨酸激酶抑制剂联合免疫检查点抑制剂在中晚期肝细胞癌 二线治疗中的效果及安全性分析.

Objective To investigate the efficacy and safety of tyrosine kinase inhibitor (TKI)combined with immune checkpoint inhibitor as the second-line therapy for advanced hepatocellular carcinoma (HCC). Methods A retrospective analysis was performed for the clinical data of 63 patients with advanced HCC who were admitted to Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, from January 2018 to December 2022, and all patients experienced progression/intolerance after transcatheter arterial chemoembolization combined with first-line TKI and were switched to secondline TKI with or without immune checkpoint inhibitor. The 32 patients receiving second-line TKI with immune checkpoint inhibitor were enrolled as combination group, and the 31 patients receiving second-line TKI alone were enrolled as single treatment group. Modified Response Evaluation Criteria in Solid Tumors was used to evaluate tumor response, and Common Terminology Criteria for Adverse Events 5.0 was used to evaluate adverse events. The Kaplan-Meier method was used to calculate median overall survival (mOS)and median progression-free survival (mPFS)for the two groups, and the two groups were compared in terms of objective response rate (ORR)and disease control rate (DCR). The chi-square test was used for comparison of baseline data and follow-up results between groups. Results The median follow-up time was 16.5(3.2 — 53.4)months for the 63 patients. The combination group had an mOS of 24.3(95% confidence interval ［CI］：20.0—28.6)months and an mPFS of 9.8(95%CI：7.5—12.1)months, while the single treatment group had an mOS of 15.8(95%CI：11.4—20.1)months and an mPFS of 4.1(95%CI：3.2—4.9)months, and there were significant differences in mOS and mPFS between the two groups (P=0.029 and 0.038). The combination group had an ORR of 47% and a DCR of 84%, while the single treatment group had an ORR of 19% and a DCR of 65%； there was a significant difference in ORR between the two groups (P=0.021), but with no significant difference in DCR between the two groups (P= 0.070). As for adverse events, 4 patients (12.5%)in the combination group and 3(10.0%)in the single treatment group experienced grade Ⅲ — Ⅳ serious adverse events, with no fatal drug reactions in either group, and there was no significant difference in the incidence rate of adverse events between the two groups (P=0.783). Conclusion Compared with TKI alone, TKI combined with immune checkpoint inhibitor has a more significant therapeutic effect as the second-line therapy for advanced HCC, without increasing serious adverse reactions [ABSTRACT FROM AUTHOR]