Comparison of drug-eluting bead transarterial chemoembolization combined with apatinib versus drug-eluting bead transarterial chemoembolization for the treatment of unresectable hepatocellular carcinoma: a randomized, prospective, multicenter phase III trial

Abstract

This randomized, prospective, multicenter (12 centers in China) phase III trial (Chinese Clinical Trial Registry #ChiCTR2000041170) compared drug-eluting bead transarterial chemoembolization (DEB-TACE) combined with apatinib and DEB-TACE monotherapy for patients with unresectable hepatocellular carcinoma (uHCC). Progression-free survival (PFS) was the primary endpoint. Overall survival (OS), mRECIST-based objective response rates (ORR) and disease control rates (DCR), and treatment-related adverse events (TRAEs) were secondary endpoints. Totally 243 cases were randomized, with 122 and 121 in the DEB-TACE + apatinib and DEB-TACE groups, respectively. Cases administered DEB-TACE + apatinib displayed markedly improved median PFS (7.1 months [95%CI 6.6-8.3] vs. 5.2 months [95%CI 5.0-5.9]) and OS (23.3 months [95%CI 20.7-29.6] vs. 18.9 months [95%CI 17.9-20.1] compared with those treated with DEB-TACE (both p < 0.001). Additionally, patients administered DEB-TACE + apatinib had elevated ORR (56.6% vs. 38.8%) and DCR (89.3% vs. 80.2%) versus the DEB-TACE group (both p < 0.001). Majority of TRAEs were mild and manageable. Regarding DEB-TACE-related TRAEs, the rates of hepatic artery thinning and spasms were elevated during the second DEB-TACE in cases administered DEB-TACE + apatinib vs. DEB-TACE. The commonest apatinib-related TRAEs in the DEB-TACE + apatinib group included hypertension, hand-foot syndrome, fatigue, and diarrhea. In conclusion, DEB-TACE plus apatinib demonstrates superior PFS versus DEB-TACE monotherapy in uHCC cases, maintaining a favorable safety profile with similar occurrences of AEs.

Fig. 1

Study flowchart. Abbreviations: DEB-TACE, Drug-eluting bead transarterial chemoembolization; D + apatinib, DEB-TACE plus apatinib; ITT, intention-to-treat population

Fig. 2

Kaplan-Meier curves for overall survival (a, c, and e) and progression-free survival (b, d, and f) estimation in both groups in all patients (a, b) and in cases with BCLC B (c, d), and BCLC C (e, f) lesions. Median (95%CI). DEB-TACE Drug-eluting bead transarterial chemoembolization, D + apatinib, DEB-TACE plus apatinib, BCLC Barcelona clinic liver cancer, P value for the log-rank test

Fig. 3

Images in a 59-year-old man with advanced hepatocellular carcinoma. a Hepatic angiography during the first TACE. b In the first DEB-TACE, CalliSpheres@ Beads with a diameter of 100-300 um loaded with 60 mg of doxorubicin were used to embolize the right hepatic artery, and the VL phenomenon occurred in the re-examination angiography (arrow). c PVA particles with a diameter of 350-560 μm were subsequently added for embolization until the VL phenomenon disappeared in the re-examination angiography. d Enhanced MRI at 4 weeks after the first DEB-TACE revealed partial contrast enhancement in the peripheral intrahepatic lesion, suggesting a partial response according to mRECIST criteria. Each small division on the scale bar represents 1 cm. e After 3 rounds of DEB-TACE plus apatinib, MR images at 6 months of follow-up show that the tumor had a complete response. Each small division on the scale bar represents 1 cm. f One-year follow-up MR images show that the tumor had a complete response. Each small division on the scale bar represents 1 cm