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

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

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.

Keywords: apatinib; capecitabine; first-line treatment; hepatocellular carcinoma; immune checkpoint inhibitors; sintilimab.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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

Associated data

  • ClinicalTrials.gov/NCT04411706