As reported in The Lancet Oncology by Qin et al, the final analysis of the phase III CARES-310 trial has shown superior overall survival with camrelizumab plus rivoceranib vs sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma.
Initial reports from the study showed significant improvements in progression-free survival (primary analysis) and overall survival (interim analysis) with camrelizumab plus rivoceranib.
Study Details
In the open-label international trial, 543 patients from sites in 13 countries and regions were randomly assigned between June 2019 and March 2021 to receive the anti–PD-1 antibody camrelizumab at 200 mg every 2 weeks plus the VEGFR2 inhibitor rivoceranib at 250 mg once daily (n = 272) or sorafenib at 400 mg twice daily (n = 271). Treatment continued until progression or unacceptable toxicity. Overall, 83% of patients in each group were Asian. The primary endpoints were progression-free survival on blinded independent review committee assessment and overall survival in the intention-to-treat population.
Key Findings
At final analysis in June 2023, median follow-up was 22.1 months (interquartile range [IQR] = 11.9–30.3 months) in the camrelizumab plus rivoceranib group and 14.9 months (IQR = 7.2–28.3 months) in the sorafenib group.
On final analysis, median overall survival was 23.8 months (95% confidence interval [CI] = 20.6–27.2 months) in the camrelizumab plus rivoceranib group vs 15.2 months (95% CI = 13.2–18.5 months) in the sorafenib group (hazard ratio [HR] = 0.64, 95% CI = 0.52–0.79, P < .0001). In a post hoc landmark analysis, rates at 12, 24, and 36 months were 77% vs 61%, 49% vs 33%, and 38% vs 25%.
With extended follow-up, median progression-free survival was 5.6 months (95% CI = 5.5–7.4 months) in the camrelizumab plus rivoceranib group vs 3.7 months (95% CI = 3.1–3.7 months) in the sorafenib group (HR = 0.54, 95% CI = 0.44–0.67, P < .0001). Subsequent systemic anticancer therapy was administered in 44% vs 57% of patients, most commonly targeted therapy (36% vs 42%) and immunotherapy (17% vs 36%).
Overall, grade 3 or worse treatment-related adverse events occurred in 81% of the camrelizumab plus rivoceranib group vs 54% of the sorafenib group. The most common grade 3 or 4 treatment-related adverse events were hypertension (38% vs 15%), palmar-plantar erythrodysesthesia syndrome (12% vs 16%), and increased aspartate aminotransferase (17% vs 5%). Treatment-related serious adverse events occurred in 25% vs 7% of patients. Treatment-related death occurred in one patient in the camrelizumab plus rivoceranib group (due to multiple organ dysfunction syndrome) and one patient in the sorafenib group (due to respiratory failure and circulatory collapse).
The investigators concluded: “At final analysis, camrelizumab plus rivoceranib continued to show clinically meaningful survival improvement compared with sorafenib, with manageable safety. The extended follow-up further confirmed the benefit-to-risk profile of camrelizumab plus rivoceranib, supporting the combination as a new first-line treatment option for unresectable hepatocellular carcinoma.”
Shukui Qin, MD, of Cancer Centre of Jinling Hospital, Nanjing University of Chinese Medicine and Nanjing Medical University, Nanjing, China, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Jiangsu Hengrui Pharmaceuticals and Elevar Therapeutics. For full disclosures of all study authors, visit thelancet.com.
