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

Abstract

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/m2, 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.

• Authors: Dailong Li, Lu Xu, Jinxing Ji, Dan Bao, Juan Hu, Ying Qian, Yinjie Zhou, Zhuo Chen, Daojun Li, Xiaopeng Li, Xiaoling Zhang, Hao Wang, Changjun Yi, Menglu Shi, Yaqi Pang, Siqi Liu, Xinhua Xu
• Journal: Frontiers in immunology (Front Immunol) Vol. 13 Pg. 944062 ( 2022) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 36091003 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Li, Xu, Ji, Bao, Hu, Qian, Zhou, Chen, Li, Li, Zhang, Wang, Yi, Shi, Pang, Liu and Xu.

Chemical References

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• Pyridines
• apatinib
• Capecitabine
• sintilimab

Topics

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents (therapeutic use)
• Capecitabine (adverse effects)
• Carcinoma, Hepatocellular (drug therapy, pathology)
• Humans
• Liver Neoplasms (drug therapy)
• Prospective Studies
• Pyridines
• Treatment Outcome