Transarterial Chemoembolization Combined With Camrelizumab and Rivoceranib for Unresectable Hepatocellular Carcinoma (CHANCE2005/CARES-005): A Randomized Phase II Trial.

[PURPOSE] Transarterial chemoembolization (TACE) alone has shown limited efficacy in improving survival among patients with unresectable hepatocellular carcinoma (HCC). This phase II trial compared TACE combined with camrelizumab (anti-PD-1 antibody) and rivoceranib (vascular endothelial growth factor receptor 2 inhibitor) versus TACE in unresectable HCC.

[METHODS] Patients with unresectable HCC (Barcelona Clinic Liver Cancer stage A to C without extrahepatic metastases) and Child-Pugh class A liver function were randomly assigned (1:1), stratified by macrovascular invasion, previous tyrosine kinase inhibitor treatment, and number of previous TACE procedures, to receive TACE combined with camrelizumab (200 mg once every 3 weeks) and rivoceranib (250 mg once daily; TACE-C-R) or TACE alone. The primary end point was progression-free survival (PFS) per composite criteria (progression per Response Evaluation Criteria in Cancer of the Liver version 5, transient deterioration to Child-Pugh class C, or TACE failure or refractoriness) in the intention-to-treat population.

[RESULTS] Between December 28, 2020, and October 29, 2023, 200 patients were randomly assigned (100 in each group). Median PFS per composite criteria was significantly longer with TACE-C-R than with TACE (10.8 months [95% CI, 8.8 to 13.7] 3.2 months [95% CI, 2.4 to 4.2]; hazard ratio, 0.34 [95% CI, 0.24 to 0.50], < .001). Grade ≥3 treatment-related adverse events occurred in 74.5% (70 of 94) of patients with TACE-C-R and 22.3% (23 of 103) of patients with TACE, with the most common being increased AST (29 [30.9%] and 13 [12.6%]) and increased ALT (23 [24.5%] and 14 [13.6%]).

[CONCLUSION] The addition of camrelizumab and rivoceranib to TACE showed statistically significant improvement in PFS for patients with unresectable HCC, with a manageable safety profile. Follow-up for further overall survival analysis is ongoing.