Comparison of camrelizumab combined with rivoceranib and sorafenib in first-line treatment of unresectable hepatocellular carcinoma

Final analysis from the CARES-310 phase III trial showed that Camrelizumab plus Rivoceranib had better overall survival than Sorafenib/Nexavar in the first-line treatment of patients with unresectable hepatocellular carcinoma. Preliminary reports from the study show a significant improvement in progression-free survival (preliminary analysis) and overall survival (interim analysis) with Camrelizumab combined with Rivoceranib.

In this open-label international trial, 543 patients from 13 countries and regions were randomly assigned to receive 200 mg every 2 weeks between June 2019 and March 2021. The anti-PD-1 antibody camrizumab, plus 250 mg of the VEGFR2 inhibitor rivoceranib once daily (n=272) or 400 mg of sorafenib twice daily (n=271). Treatment was continued until progression or unacceptable toxicity. Overall, 83% of patients in each group were Asian. The primary endpoints were progression-free survival as assessed by a blinded independent review committee and overall survival in the intention-to-treat population.

In the final analysis in June 2023, the median follow-up time for the Camrelizumab plus Rivoceranib group was 22.1 months (interquartile range [IQR] = 11.9-30.3 months) and the sorafenib group was 14.9 months (IQR = 7.2-28.3 months). Final analysis, Camrelizumab plus Rivoceranib The median overall survival was 23.8 months (95% confidence interval [CI] = 20.6-27.2 months) in arm b and 15.2 months (95% CI = 13.2-18.5 months) in the sorafenib arm (hazard ratio [HR] = 0.64, 95% CI=0.52-0.79, P<0.0001). In post hoc landmark analyses, incidence rates at 12, 24, and 36 months were 77% vs. 61%, 49% vs. 33%, and 38% vs. 25%, respectively.

With the extension of follow-up time,The median progression-free survival of the Camrelizumab combined with Rivoceranib group was 5.6 months (95%CI=5.5-7.4 months), the sorafenib group was 3.7 months (95%CI=3.1-3.7 months) (HR=0.54, 95%CI=0.44-0.67, P<0.0001). 44% and 57% of patients received subsequent systemic anticancer therapy, most commonly targeted therapy (36% and 42%) and immunotherapy (17% and 36%).

Overall,81% of patients in the Camrelizumab plus Rivoceranib group experienced grade 3 or worse treatment-related adverse events, compared with 54% in the sorafenib group. The most common grade 3 or 4 treatment-related adverse events were hypertension (38% vs. 15%), palmoplantar dysesthesia syndrome (12% vs. 16%), and aspartate aminotransferase elevation (17% vs. 5%). Treatment-related serious adverse events occurred in 25% and 7% of patients. Treatment-related deaths occurred in one patient in the kamalizumab plus rivatranib group (due to multiple organ dysfunction syndrome) and in one patient in the sorafenib group (due to respiratory failure and circulatory failure).

Therefore, Camrelizumab combined with Rivoceranib continues to show a clinically meaningful improvement in survival compared with sorafenib, with a manageable safety profile. Extended follow-up further confirmed the benefit of camrelizumab plus rivoceranib on risk profile, supporting this combination as a new first-line treatment option for unresectable hepatocellular carcinoma.

References:https://ascopost.com/news/december-2025/camrelizumab-plus-rivoceranib-vs-sorafenib-for-the-first-line-treatment-of-unresectable-hepatocellular-carcinoma/