Adding camrelizumab and rivoceranib to transarterial chemoembolization (TACE) significantly prolonged progression-free survival (PFS) in patients with unresectable hepatocellular carcinoma (HCC), according to the CARES-005 study presented at the American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium. The combination demonstrates a potential new treatment option for patients with this challenging cancer.
Improved Progression-Free Survival
At a median follow-up of 13.6 months, the median PFS was 10.8 months with TACE plus camrelizumab and rivoceranib (TACE-CR) compared to 3.2 months with TACE alone (HR 0.34, 95% CI 0.24-0.50, P<0.0001). The 6-month PFS rate was 70.8% with TACE-CR and 31.5% with TACE alone, demonstrating a clinically meaningful and statistically significant improvement.
Gao-Jun Teng, MD, of Zhongda Hospital, Southeast University, noted that the study showed a significant improvement in PFS for unresectable HCC patients who received TACE plus immunotherapy-based systemic treatment, compared to TACE alone.
Objective Response and Disease Control
Objective response rates (ORR) and disease control rates (DCR) were also significantly higher in the TACE-CR group. Per RECICL criteria, ORR was 65.0% and DCR was 87.0% in the TACE-CR group, compared to 30.0% and 63.0% in the TACE group, respectively. The duration of response was 11.4 months in the TACE-CR group and 6.9 months in the TACE group.
Overall Survival Trend
While overall survival (OS) data were immature, there was a trend towards improved OS in the ITT population, with a median of 24.0 months in the TACE-CR group versus 21.5 months in the TACE alone group (HR 0.87, 95% CI 0.57-1.32). The 12-month OS rates were 74.5% and 66.2%, respectively.
Background and Rationale
TACE has been a standard treatment for intermediate HCC, but long-term survival has been limited. Combining TACE with immunotherapy-based treatment can potentially enhance antitumor efficacy by activating the immune system, converting “cold tumors” to “hot tumors” that respond to immunotherapy. Similar regimens have shown success in trials like EMERALD-1 and LEAP-012.
Study Details
The CARES-005 study was a multicenter, randomized, controlled phase 2 trial conducted at 23 sites in China, involving 200 patients with unresectable HCC eligible for embolization. Patients were randomized to receive either TACE-CR or TACE alone. The median age was 58.5 in the TACE-CR group and 57 in the TACE group, with both groups being predominantly male (87%).
Safety Profile
The safety profile for TACE-CR was manageable and consistent with the known adverse event profiles of TACE, camrelizumab, and rivoceranib in unresectable HCC. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 76.6% of patients with TACE-CR and 24.3% of patients with TACE alone. The most common grade ≥3 TRAEs in the TACE-CR group were increased aspartate aminotransferase (AST, 30.9%), increased alanine aminotransferase (ALT, 24.5%), hypertension (13.8%), and decreased platelet count (11.7%).
Regulatory Context
In 2024, the FDA accepted a resubmission of a new drug application for the combination of camrelizumab and rivoceranib as a standard first-line treatment for HCC unsuitable for resection, based on the CARES-310 study. Rivoceranib, under the name apatinib (Aitan), was approved in gastric cancer in China in 2014 and in combination with camrelizumab for unresectable HCC in 2023.
