信迪利单抗联合仑伐替尼二线治疗不可切除肝细胞肝癌的临床疗效及安全性

Efficacy and safety of sintilimab in combination with lenvatinib therapy as second-line regimen for patients with unresectable hepatocellular carcinoma

目的分析信迪利单抗联合仑伐替尼二线治疗不可切除肝细胞癌(hepatocellular carcinoma,HCC)的临床疗效及安全性。方法回顾性纳入39例接受信迪利单抗联合仑伐替尼、36例单用仑伐替尼二线治疗的中晚期HCC患者。收集患者治疗基线的血常规、肝功能、肾功能、肿瘤分期、肿瘤影像学特征、既往接受的治疗策略等临床资料,定期随访患者的影像学复查结果、治疗过程中出现的不良反应,直至患者随访截止或失访或死亡。使用mRECIST标准评价疗效,Kaplan-Meier法绘制生存曲线。结果截至末次随访,两组患者均未获得CR。39例患者接受信迪利单抗联合仑伐替尼治疗后,15例(38.4%)例获得部分缓解,14例(35.9%)获得疾病稳定,10例(25.8%)疾病进展;ORR为38.5%;DCR为74.4%。36例患者单用仑伐替尼治疗后,6例(16.7%)获得部分缓解,14例(35.8%)获得疾病稳定,10例(25.8%)疾病进展;ORR为38.5%;DCR为74.4%。联合治疗组中位PFS时间为9.1个月(95%CI:7.5~10.7),仑伐替尼单药组中位PFS时间为5.9个月(95%CI:4.7~7.1);两组间PFS比较差异有统计学意义(P<0.001)。联合治疗组中位OS时间为18.4个月(95%CI:16.5~20.3),仑伐替尼单药组中位OS时间为11.6个月(95%CI:7.2~16.0);两组间OS比较差异有统计学意义(P=0.016)。3级以上不良事件主要有高血压、腹泻,不良反应均得到有效控制。结论信迪利单抗联合仑伐替尼治疗可有效延长中晚期肝癌患者的生存期,严重不良反应发生率低,是一种安全、有效的治疗方案。

Objective To analysis the efficacy and tolerability of sintilimab in combination with lenvatinib therapy as second-line regimen for patients with hepatocellular carcinoma(HCC).Methods We retrospectively analyzed the data of 39 patients with unresectable HCC treated with sintilimab in combination with lenvatinib as second-line therapy,as well as the data of another 36 patients treated with lenvatinib therapy as contrast.The clinical data such as the baseline data from blood routine test liver function test,renal function test tumor staging,tumor imaging features,previous treatment strategies,follow-up imaging results and adverse events during follow-ups were recorded.The Modified Response Evaluation Criteria in Solid Tumors was used to evaluate the treatment outcome of intrahepatic lesions and the Kaplan-Meier method was used to evaluate survival time.Results All through the follow-ups,the treatments for the patients from both groups did not reached complete response.Among the 39 patients treated with sintilimab plus lenvatinib,15 cases achieved partial remission(PR),accounting for 38.4%,14 disease stability(DS),accounting for 35.9%,and 10 progressive disease,accounting for 25.8%,with the ORR and DCR of 38.5%and 74.4%,respectively.Among the 36 patients in the control group,6 cases achieved partial remission,accounting for 16.7%,14 disease stability,accounting for 35.8%,and 10 progressive disease,accounting for 25.8%,with the ORR and DCR of 38.5%and 74.4%,respectively.The median progression-free survival(PFS)was 9.1 months in the combination group(95%CI:7.5~10.7)and 5.9 months(95%CI:4.7~7.1)in the control group,with a statistically significant difference between the two groups(P<0.001).Median Overall Survival(OS)time in the combination group was 18.4 months(95%CI:16.5~20.3)and 11.6 months(95%CI:7.2~16.0)in the control group,with a statistical difference between the two groups(P=0.016).Grade≥3 treatment-related adverse events(TRAEs)included hypertension and diarrhea.All TRAEs were effectively controlled.Conclusion Sintilimab combined with lenvatinibcan yield a promising outcome in treating the patients with unresectable HCC for its low incidence rate of serious adverse eventsand thus it is a safe and effective treatment regimen.