The combination of rivoceranib and camrelizumab continues to demonstrate a clinically significant survival advantage over sorafenib in patients with advanced, unresectable hepatocellular carcinoma (HCC). These findings, from the final analysis of the phase 3 CARES-310 trial, were presented at the 2024 ASCO Annual Meeting, reinforcing the potential of this combination as a first-line treatment option.
Sustained Overall Survival Benefit
At a median follow-up of 22.1 months in the combination arm and 14.9 months in the sorafenib arm, the median overall survival (OS) was 23.8 months (95% CI, 20.6-27.2) for the camrelizumab plus rivoceranib group (n = 272) compared to 15.2 months (95% CI, 13.2-18.5) for the sorafenib group (n = 271). This translated to a hazard ratio of 0.64 (95% CI, 0.52-0.79; 1-sided P <.0001), indicating a significant reduction in the risk of death. Notably, the 24-month and 36-month OS rates were 49.0% and 37.7% for the combination, respectively, versus 32.6% and 24.8% for sorafenib.
Progression-Free Survival Improvement
The study also demonstrated a significant improvement in progression-free survival (PFS) with the combination therapy. The median PFS was 5.6 months (95% CI, 5.5-7.4) for the camrelizumab plus rivoceranib group compared to 3.7 months (95% CI, 3.1-3.7) for the sorafenib group (HR, 0.54; 95% CI, 0.44-0.67; P <.0001).
Objective Response Rate and Safety
The objective response rate (ORR) was significantly higher in the combination arm, with 26.8% (95% CI, 21.7%-32.5%) of patients achieving a response compared to only 5.9% (95% CI, 3.4%-9.4%) in the sorafenib arm. The median duration of response was 17.5 months (95% CI, 9.3-NR) for the combination group versus 9.2 months (95% CI, 5.3-NR) for the sorafenib group.
Safety data from the trial remained consistent with previous findings, with no new safety signals identified. Treatment-related adverse events (TRAEs) leading to discontinuation of camrelizumab and rivoceranib were 17.6% and 16.9%, respectively, in the combination group, with a 4.4% discontinuation rate for both agents. In the sorafenib group, the discontinuation rate due to TRAEs was 4.8%.
Common TRAEs in the combination group included hypertension (69.5%), increased aspartate aminotransferase (AST; 54.8%), and proteinuria (49.6%). In the sorafenib group, common TRAEs included palmar-plantar erythrodysesthesia (PPE) syndrome (61.0%) and diarrhea (39.4%).
Study Design and Patient Population
The CARES-310 trial was an international, randomized, open-label study that enrolled patients with unresectable or metastatic HCC, classified as Barcelona Clinic Liver Cancer (BCLC) stage B or C, who had not received prior systemic therapy. Patients were randomized 1:1 to receive either camrelizumab (200 mg IV every 2 weeks) plus rivoceranib (250 mg daily) or sorafenib (400 mg twice daily).
The primary endpoints of the study were PFS and OS, with ORR as a key secondary endpoint. Key stratification factors included the presence of macrovascular invasion (MVI) or extrahepatic spread (EHS), geographic region, and baseline serum alpha-fetoprotein levels.
Expert Commentary
"The extended follow-up further confirmed the favorable benefit-to-risk profile of camrelizumab plus rivoceranib, supporting it as a new first-line treatment option for unresectable HCC," said Arndt Vogel, MD, a professor of medicine at the University of Toronto and a clinician scientist at the Toronto Centre for Liver Disease.
