Transarterial chemoembolization plus apatinib for unresectable hepatocellular carcinoma: a multicenter, randomized, open-label, phase III trial

BMC Med. 2025 May 28;23(1):313. doi: 10.1186/s12916-025-04159-y.

Abstract

Background: This study aimed to assess the efficacy and safety of transarterial chemoembolization (TACE) in combination with apatinib (TACE-apatinib) for patients with unresectable hepatocellular carcinoma (HCC).

Methods: This study was a multicenter, randomized, open-label, prospective, phase III trial. Patients with unresectable HCC were randomly assigned in a 1:1 ratio to receive either TACE-apatinib or TACE-alone treatment. Patients in the TACE-apatinib group began with a dosage of 500 mg/day of oral apatinib administered 4 days after the first TACE. The primary endpoint of this study was progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), time to untreatable (unTACEable) progression (TTUP), and safety assessment.

Results: From November 1, 2018 to November 18, 2021, a total of 196 patients were randomly assigned to either the TACE-apatinib (n = 86) or TACE-alone (n = 92) group. The median PFS in the TACE-apatinib group was significantly longer than that of in the TACE-alone group (6.1 months vs. 3.4 months, p < 0.0001). The median OS was significantly prolonged in the TACE-apatinib group compared to the TACE-alone group (28.9 months vs. 24.0 months, p = 0.0005). The median TTUP in the TACE-apatinib group was 26.8 months, which was significantly longer than that of 20.1 months in the TACE-alone group (p = 0.0003). A significantly higher ORR and DCR were observed in the TACE-apatinib group compared to the TACE-alone group (ORR: 58.1% vs. 31.5%, p < 0.001; DCR: 87.2% vs. 69.6%, p = 0.004). Most of the treatment-related adverse events were grades 1-2, and no treatment-related deaths were observed.

Conclusions: Apatinib significantly improved the treatment effects of TACE for patients with unresectable HCC. TACE-apatinib could serve as a promising treatment option for this patient population, offering notable survival benefits while maintaining an acceptable safety profile.

Trial registration: Chinese Clinical Trial Register, No. ChiCTR1800018621.

Keywords: Apatinib; Hepatocellular carcinoma; Progression free survival; Transarterial chemoembolization.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents* / administration & dosage
  • Antineoplastic Agents* / adverse effects
  • Antineoplastic Agents* / therapeutic use
  • Carcinoma, Hepatocellular* / mortality
  • Carcinoma, Hepatocellular* / therapy
  • Chemoembolization, Therapeutic* / adverse effects
  • Chemoembolization, Therapeutic* / methods
  • Combined Modality Therapy
  • Female
  • Humans
  • Liver Neoplasms* / mortality
  • Liver Neoplasms* / therapy
  • Male
  • Middle Aged
  • Prospective Studies
  • Pyridines* / administration & dosage
  • Pyridines* / adverse effects
  • Pyridines* / therapeutic use
  • Treatment Outcome

Substances

  • apatinib
  • Pyridines
  • Antineoplastic Agents