Combined Camrelizumab and Rivoceranib Improves Event-Free Survival in Resectable Hepatocellular Carcinoma

A clinical trial has found that a perioperative treatment regimen combining camrelizumab and rivoceranib significantly improves event-free survival for patients with resectable hepatocellular carcinoma who face an intermediate or high risk of recurrence.

According to research published in The Lancet and detailed in the CARES-009 trial, this combined approach outperformed surgery alone in extending the time patients remained free of disease events.

The study reported that the median event-free survival for the perioperative group was 42.1 months, with a 95% confidence interval ranging from 23.2 to not estimable. In comparison, patients who underwent surgery alone had a median event-free survival of 19.4 months, with a 95% confidence interval ranging from 14.9 to not estimable.

The CARES-009 Trial Design

The CARES-009 trial was a multicentre, open-label, randomised, phase 2/3 trial conducted across 16 hospitals in China. Between March 25, 2021, and January 29, 2024, the study enrolled 294 patients.

The participant cohort consisted of 87% male patients, and 99% of the participants were Han Chinese. These patients were randomly assigned in a 1:1 ratio to receive either the perioperative therapy or surgery alone, with stratification based on hepatitis B virus infection status and China Liver Cancer Staging (CNLC) stage.

The primary endpoint of the study was event-free survival (EFS), which was assessed by investigators in the intention-to-treat population. Safety evaluations were conducted within the as-treated population.

Patient Eligibility and Criteria

The trial specifically targeted patients with resectable hepatocellular carcinoma classified as CNLC stage Ib-IIIa. A key requirement for eligibility was the absence of Vp4 portal vein tumour thrombosis.

These classifications correspond to the following Barcelona Clinic Liver Cancer (BCLC) stages:

• BCLC stage A with a tumour larger than 5 cm.
• BCLC stage B.
• BCLC stage C, provided there was no Vp4 involvement or extrahepatic metastasis.

The Perioperative Treatment Protocol

The perioperative group followed a structured sequence of immunotherapy and surgery designed to reduce tumour burden and mitigate the risk of cancer returning after the operation.

The protocol consisted of three distinct phases:

• Neoadjuvant therapy: Patients received two cycles of camrelizumab plus rivoceranib before undergoing surgery.
• Surgical intervention: Patients underwent radical surgical resection.
• Adjuvant therapy: Following surgery, patients continued treatment with camrelizumab plus rivoceranib.

This approach differs from the standard curative approach, which typically relies on surgical resection alone for early-stage hepatocellular carcinoma.

Medical Context and Challenges

While surgical resection is the preferred curative method for early-stage hepatocellular carcinoma, the high rate of recurrence remains a primary challenge for clinicians and patients.

Because of this risk, researchers have explored neoadjuvant therapies to shrink tumours before surgery and adjuvant therapies to eliminate remaining microscopic disease afterward. The use of camrelizumab, an immunotherapy, combined with rivoceranib is intended to address these recurrence risks in populations identified as high or intermediate risk.

The CARES-009 trial is registered with ClinicalTrials.gov under the identifier NCT04521153 and is currently listed as ongoing.