Transarterial embolization plus hepatic arterial infusion chemotherapy combined with rivoceranib and camrelizumab for initially unresectable hepatocellular carcinoma with high tumor burden: A single-arm, prospective, multicenter study.

e16156 Background: In recent years, combination treatment strategies incorporating transarterial locoregional therapies with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) for patients with unresectable hepatocellular carcinoma (uHCC) have gained increasing attention. Multiple multicenter retrospective studies have confirmed that treatment regimens combining transarterial chemoembolization plus hepatic arterial infusion chemotherapy (TACE+HAIC) with TKIs and ICIs are associated with significant efficacy and a manageable safety profile. The present study aims to evaluate the efficacy and safety of transarterial embolization plus hepatic arterial infusion chemotherapy (TAE+HAIC) combined with rivoceranib and camrelizumab as a first-line treatment for patients with initially uHCC with high tumor burden (uHTB-HCC). Methods: This single-arm, prospective, multicenter study enrolled patients with initially diagnosed uHTB-HCC who met at least one of the following criteria: (1) a high tumor burden defined as the sum of the number of tumors and the size of the largest tumor exceeding 11, based on criteria 7–11; or (2) the presence of portal vein tumor thrombus classified as VP3–VP4. All enrolled patients received TAE+HAIC, followed by camrelizumab (200 mg every 3 weeks) in combination with rivoceranib (250 mg/day). The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression free survival (PFS), overall survival (OS), and safety. This study was registered at ClinicalTrials.gov (NCT06363825). Results: Between April 15, 2024, and August 7, 2025, a total of 51 patients were enrolled across five centers and received the triple-combination therapy (TAE+HAIC+Camrelizumab+Rivoceranib). The cohort comprised 44 men and 7 women, with a mean age of 57.9 ± 9.9 years. Portal vein tumor thrombosis was present in 38 patients (74.5%), and 11 patients (23.5%) had extrahepatic metastases. As of the data cutoff on December 31, 2025, the median follow-up duration was 10.3 months (IQR, 6.1–11.4). According to RECIST1.1 criteria, the ORR was 64.7% and the DCR was 80.4%. Based on mRECIST criteria, the ORR was 78.4% and the DCR remained 80.4%. Notably, 12 patients (23.5%) were successfully converted to surgical resection. The mPFS was 9.2 months (95% CI, 4.0–14.5), while the mOS has not yet been reached. 36 patients (70.5%) had treatment-related adverse event (TRAEs) that were grade 3-5, but no treatment-related deaths were reported. Conclusions: The combination therapy (TAE+HAIC+Camrelizumab+Rivoceranib) significantly improved ORR and PFS in patients with uHTB-HCC, with a manageable safety profile. Further large-scale randomized trials are warranted to validate these findings. Clinical trial information: NCT06363825 .