索拉非尼联合免疫检查点抑制剂治疗TACE抵抗的中晚期肝癌的疗效及安全性

目的 探讨索拉非尼联合免疫检查点抑制剂（immune checkpoint inhibitors，ICIs）治疗经肝动脉化疗栓塞术（transcatheter arterial chemoembolization，TACE）抵抗的中晚期肝癌的疗效及安全性。方法 回顾性分析2017年1月至2021年3月期间在温州医科大学附属第五医院确诊为TACE抵抗的中晚期肝癌患者的资料，共54例，年龄28～82（56.1±11.8）岁，其中BCLC B期24例，C期30例；Child-Pugh A级34例，B级20例。根据治疗方法不同，分为对照组和联合组，对照组接受单一索拉非尼治疗（n=33），联合组接受索拉非尼联合ICIs治疗（n=21）；比较两组患者的一般情况、肿瘤反应性、肿瘤无进展生存时间（progression-free survival，PFS）及不良反应的发生情况。结果 联合组（2例CR、11例PR、4例SD和4例PD）的肿瘤反应性明显优于对照组（2例CR、8例PR、10例SD、13例PD）（P=0.041）。联合组的中位PFS明显长于对照组（13.5个月 vs 6.8个月，P=0.010）；多因素分析显示Child-Pugh B级（HR 2.202，95%CI 1.059～4.581，P=0.035）、BCLC C期（HR 4.077，95%CI 1.902～8.742，P<0.001）、AFP≥400 ng/mL（HR 5.728，95%CI 2.227～14.729，P＜0.001）是TACE抵抗肝癌PFS的独立危险因素，索拉非尼联合ICIs（HR 0.180，95%CI 0.082～0.392，P<0.001）是肝癌患者的保护因素。联合组并发皮炎、腹泻的发生率明显多于对照组（P<0.05）。结论 索拉非尼联合ICIs治疗提高TACE抵抗中晚期肝癌的肿瘤反应性，延长患者PFS，是一种有效、安全的治疗方案。

Efficacy and safety of sorafenib combined with immune checkpoint inhibitors in TACE refractory liver cancer

Objective To investigate the efficacy and safety of sorafenib combined with immune checkpoint inhibitors (ICIs) in treatment of transcatheter arterial chemoembolization (TACE) refractory liver cancer. Methods A total of 54 patients with TACE refractory liver cancer were collected in the Fifth Affiliated Hospital of Wenzhou Medical University from Jan. 2017 to Mar. 2021. The 54 patients including 24 cases of BCLC stage B and 30 cases of stage C, 34 cases of child Pugh grade A and 20 cases of grade B, with an average age of (56.1±11.8), ranging from 28 to 82 years were classified into control group and combined group according to the different therapies. Patients in control group (n=33 cases) received sorafenib alone, while patients in combined group (n=21 cases) received sorafenib combined with ICIs after suffering from TACE refractory. The difference of clinical charateristics, tumor response, progression-free survival (PFS) and adverse events in the two groups were compared. Results Tumor response of the combined group (2 CR, 11 PR, 4 SD and 4 PD) was significantly better than that of the control group (2 CR, 8 PR, 10 SD and 13 PD) (P=0.041). The median progression-free survival (PFS) of the combined group was significantly longer than that of the control group (13.5 months vs 6.8 months, P=0.010). Multivariate analysis showed that Child Pugh B (HR 2.202, 95%CI 1.059~4.581, P=0.035), BCLC C (HR 4.077, 95%CI 1.902~8.742, P<0.001), AFP≥400 ng/mL (HR 5.728, 95%CI 2.227~14.729, P<0.001) were independent risk factors of PFS in patients with TACE refractory liver cancer. The combination of ICIs and sorafenib (HR 0.180, 95%CI 0.082~0.392, P<0.001) was the protective factor of PFS inpatients with TACE refractory liver cancer. The incidence of dermatitis (5 vs 1 case, P=0.028) and diarrhea (5 vs 1 case, P=0.028) in the combined group was significantly higher than that in the control group. Conclusion Sorafenib combined with ICIs is an effective and safe therapy for TACE refractory liver cancer in improving tumor response and prolonging PFS.