Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide. For patients with unresectable HCC, transarterial chemoembolization (TACE) is a standard treatment. The phase 2, multicenter, open-label, randomized CARES-005 trial aimed to evaluate the efficacy and safety of TACE combined with camrelizumab and rivoceranib compared to TACE alone in treating unresectable HCC. This study was presented by Dr. Gaojun Teng from Zhongda Hospital Southeast University at the ASCO Gastrointestinal Cancers Symposium.CARES-005 was a multicenter, open-label, randomized phase 2 study enrolling 200 patients with unresectable HCC. Patients were assigned to either TACE plus camrelizumab (200 mg IV, Q3W) and rivoceranib (250 mg PO, QD) or TACE alone. The study’s primary endpoint was progression-free survival (PFS) as per RECICL criteria. Secondary endpoints included PFS per mRECIST, overall survival (OS), tumor response, and safety profile.
The median age of the study population was 58.5 years in the TACE+C+R group and 57.0 years in the TACE group. A majority (80% in TACE+C+R, 75% in TACE) were aged ≤65 years. HBV infection was the leading cause of HCC (80% in TACE+C+R, 79% in TACE). The proportion of patients with macrovascular invasion was 42.0% in TACE+C+R and 44.0% in TACE. ECOG PS 0 was observed in 56% of TACE+C+R patients and 58% of TACE patients.
Progression-Free Survival and Tumor Response
PFS per RECICL in the ITT population showed a significant improvement for TACE+C+R. The median PFS was 10.8 months (95% CI: 8.8–13.7) for TACE+C+R compared to 3.2 months (95% CI: 2.4–4.2) for TACE alone, with a hazard ratio (HR) of 0.34 (95% CI: 0.24–0.50, p < 0.0001). PFS per mRECIST was 8.8 months (95% CI: 6.2–10.8) for TACE+C+R versus 3.1 months (95% CI: 2.3–4.2) for TACE, with an HR of 0.43 (95% CI: 0.30–0.62).
Tumor responses were assessed per RECICL and mRECIST. The objective response rate (ORR) was 65.0% (95% CI: 54.8–74.3) in TACE+C+R versus 29.0% (95% CI: 20.4–38.9) in TACE under RECICL, and 61.0% (95% CI: 50.7–70.6) in TACE+C+R versus 29.0% (95% CI: 20.4–38.9) in TACE under mRECIST. The disease control rate (DCR) was 87.0% in TACE+C+R versus 63.0% in TACE under RECICL, and 85.0% versus 58.0% under mRECIST.
The median OS in the ITT population was 24.0 months (95% CI: 18.7–30.1) in TACE+C+R versus 21.5 months (95% CI: 15.6-NR) in TACE, with an HR of 0.87 (95% CI: 0.57–1.32).
Post-hoc Analysis of PFS and OS by BCLC Stage
A post-hoc analysis stratified by BCLC stage demonstrated survival benefits across different stages. For BCLC A/B, HR for PFS per RECICL was 0.34 (95% CI: 0.21–0.55), and HR for OS was 0.88 (95% CI: 0.48–1.61). For BCLC C, HR for PFS per RECICL was 0.39 (95% CI: 0.22–0.67), and HR for OS was 0.86 (95% CI: 0.48–1.53).
Safety Profile
Treatment-related adverse events (TRAEs) were reported more frequently in the combination group. The most common TRAEs (≥10% incidence) in the TACE+C+R group included AST increase (61.7%), ALT increase (55.3%), abdominal pain (42.6%), pyrexia (41.5%), blood bilirubin increase (40.4%), and platelet count decrease (37.2%). The incidence of hypertension was 25.5% in TACE+C+R versus 13.8% in TACE. While the rate of nausea, vomiting, and anemia was slightly higher in the TACE+C+R group, all adverse effects were deemed manageable.
Conclusions
The addition of camrelizumab and rivoceranib to TACE significantly improved PFS and tumor response rates compared to TACE alone. The safety profile was consistent with known profiles of immunotherapy and VEGFR inhibitors, with manageable adverse effects. These results suggest that TACE combined with camrelizumab and rivoceranib could be a promising treatment strategy for patients with unresectable HCC.
Clinical Implications
This study highlights the potential of integrating immune checkpoint inhibitors and VEGFR inhibitors with TACE to enhance treatment efficacy in unresectable HCC. Future phase 3 trials are needed to confirm these findings and establish this combination as a new standard of care.
