信迪利单抗联合阿帕替尼及卡培他滨治疗不可切除肝细胞癌：一项前瞻性、开放标签、单臂、Ⅱ期临床研究。

Sintilimab combined with apatinib plus capecitabine in the treatment of unresectable hepatocellular carcinoma: A prospective, open-label, single-arm, phase II clinical study.

机构信息

Department of Oncology, Yichang Central People's Hospital and The First College of Clinical Medical Science, China Three Gorges University, Yichang, China.

Tumor Prevention and Treatment Center of Three Gorges University and Cancer Research Institute of Three Gorges University, Yichang, China.

出版信息

Front Immunol. 2022 Aug 26;13:944062. doi: 10.3389/fimmu.2022.944062. eCollection 2022.

OBJECTIVE

To evaluate the efficacy and safety of sintilimab combined with apatinib plus capecitabine in the treatment of unresectable hepatocellular carcinoma (HCC) to provide a more effective first-line treatment for patients with advanced HCC.

METHODS

This open-label, prospective, phase II study included patients with unresectable HCC who did not receive systematic treatment. The patients were treated with sintilimab (200 mg, intravenous drip, once every 3 weeks) combined with apatinib (250 mg, oral administration, once a day) plus capecitabine (1000 mg/m, twice a day; after 2 weeks of oral administration, the drug was stopped for 1 week; course of treatment, 3 weeks). The primary endpoint was the objective response rate (ORR). The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), overall survival (OS), and safety.

RESULTS

Forty-seven patients (1 lost to follow-up) were enrolled in the study. As of March 1, 2022, the ORR and DCR were 50.0% (95% CI: 34.9-65.1%) and 91.3% (95% CI: 79.2-97.6%), respectively, after blind, independent imaging evaluation. The median follow-up time was 18.7 months (95% CI: 17.2-20.2 months). The median PFS was 9.0 months (95% CI: 7.1-10.9 months). The median DoR was 10.8 months (95% CI: 4.8-16.8 months). The median OS was not reached, and the 1-year OS rate was 71.7% (95% CI: 56.5-84.0%). Only 28.3% (13/46) of patients had grade 3/4 treatment-related adverse events.

CONCLUSION

Sintilimab combined with apatinib plus capecitabine has good safety and anti-tumor activity as a first-line treatment for unresectable HCC. This is worthy of further multi-center, prospective, randomized, large-sample clinical studies.

CLINICAL TRIAL REGISTRATION

https://ClinicalTrials.gov, identifier NCT04411706.

目的

评估信迪利单抗联合安罗替尼加卡培他滨治疗不可切除肝细胞癌（HCC）的疗效和安全性，为晚期 HCC 患者提供更有效的一线治疗方法。

方法

这是一项开放标签、前瞻性、Ⅱ期研究，纳入了未接受系统治疗的不可切除 HCC 患者。患者接受信迪利单抗（200 mg，静脉滴注，每 3 周 1 次）联合安罗替尼（250 mg，口服，每日 1 次）加卡培他滨（1000 mg/m，每日 2 次；口服 2 周后停药 1 周；疗程 3 周）治疗。主要终点为客观缓解率（ORR）。次要终点包括疾病控制率（DCR）、无进展生存期（PFS）、缓解持续时间（DoR）、总生存期（OS）和安全性。

结果

研究共纳入 47 例患者（1 例失访）。截至 2022 年 3 月 1 日，盲法独立影像学评估后，ORR 和 DCR 分别为 50.0%（95%CI：34.9%-65.1%）和 91.3%（95%CI：79.2%-97.6%）。中位随访时间为 18.7 个月（95%CI：17.2-20.2 个月）。中位 PFS 为 9.0 个月（95%CI：7.1-10.9 个月）。中位 DoR 为 10.8 个月（95%CI：4.8-16.8 个月）。中位 OS 未达到，1 年 OS 率为 71.7%（95%CI：56.5%-84.0%）。仅 28.3%（13/46）的患者发生 3/4 级治疗相关不良事件。