In a Chinese phase II/III trial (CARES-009) reported in The Lancet, Wang et al found that the addition of perioperative camrelizumab (PD-1 inhibitor) and rivoceranib (VEGFR2 inhibitor) to surgical resection significantly improved event-free survival in patients with hepatocellular carcinoma at intermediate or high risk of relapse.
Study Details
In the multicenter open-label trial, 294 patients were randomly assigned between March 2021 and January 2024 to receive perioperative therapy with surgery (n = 148) or surgery alone (n = 146). Patients had disease corresponding to Barcelona Clinic Liver Cancer stage A with tumor > 5 cm, stage B, or stage C without Vp4 portal vein involvement or extrahepatic metastasis. The perioperative group received neoadjuvant camrelizumab at 200 mg every 2 weeks and rivoceranib at 250 mg once daily for two cycles and, following surgery, adjuvant camrelizumab at 200 mg every 3 weeks plus rivoceranib at 250 mg once daily until disease progression or intolerance. The primary endpoint was investigator-assessed event-free survival in the intention-to-treat population.
Key Findings
Median event-free survival was 42.1 months (95% confidence interval [CI] = 23.2 months to not estimable) in the perioperative group vs 19.4 months (95% CI = 14.9 months to not estimable) in the surgery-alone group (hazard ratio [HR] = 0.59, 95% CI = 0.41–0.85, P = .0040). Rates at 1, 2, and 3 years were 79.5% vs 62.0%, 58.8% vs 47.4%, and 55.2% vs 39.5%. Median disease-free survival was 40.8 months (95% CI = 22.1 months to not estimable) in the perioperative group vs 19.4 months (95% CI = 14.8 months to not estimable) in the surgery-alone group (HR = 0.59, 95% CI = 0.40–0.86).
Grade 3 or worse treatment-related adverse events occurred in 38% of the perioperative group vs 0% in the surgery-alone group; the most common adverse events in the perioperative group were increased alanine aminotransferase (11%) and increased aspartate aminotransferase (11%). Treatment-related adverse events led to discontinuation of any agent in 4% of patients during neoadjuvant treatment and in 12% during adjuvant treatment. Two deaths were potentially related to treatment during neoadjuvant therapy in the perioperative group (from hepatic failure in one patient and combined hepatic and renal failure in one patient).
The investigators concluded: “Perioperative camrelizumab plus rivoceranib significantly improved [event-free survival] compared with surgery alone in patients with resectable hepatocellular carcinoma at intermediate or high risk of recurrence.”
Jian Zhou, MD, PhD, of Zhongshan Hospital, Fudan University, Shanghai, is the corresponding author of The Lancet article.
Disclosure: The study was funded by Shanghai Hospital Development Center and Jiangsu Hengrui Pharmaceuticals. For full disclosures of all study authors, visit thelancet.com.
