CARES 310 trial

Background

Phase 3, open-label RCT. 543 patients with unresectable or advanced hepatocellular carcinoma (HCC), no prior systemic therapy. Tested camrelizumab (anti-PD-1) plus rivoceranib (VEGFR2 TKI) vs sorafenib first-line.

Interventions and follow up

Arm A: Camrelizumab 200 mg IV Q2W + rivoceranib 250 mg PO QD
Arm B: Sorafenib 400 mg PO BID
Primary endpoint: PFS and OS (dual)
Median follow-up: 7.8 mo (PFS analysis)

Results

mPFS: 5.6 mo (arm A) vs 3.7 mo (arm B); HR 0.52, 95% CI 0.41–0.65, one-sided P<.0001
mOS: Significantly improved with camrelizumab + rivoceranib vs sorafenib (HR favoring arm A; specific value NR in source entry)

Adverse events

Vascular/skin: Grade 3–4 hypertension 38% (arm A) vs 15% (arm B); palmar-plantar erythrodysaesthesia 12% vs 15%
Hepatic: Grade 3–4 increased AST 17% vs 5%; increased ALT 13% vs 3%

Conclusions

Camrelizumab plus rivoceranib significantly improved PFS and OS versus sorafenib, supporting it as a new first-line option for unresectable HCC.

Key Limitations

The comparator sorafenib is now a less preferred first-line standard than atezolizumab + bevacizumab or durvalumab + tremelimumab, with which CARES-310 was not directly compared. The trial population was predominantly Asian with high hepatitis B prevalence, affecting generalizability. Hypertension and transaminase elevations were notably increased with the combination.

Clinical Context

CARES-310 added an IO + TKI doublet to the first-line HCC landscape. ESMO recognizes immunotherapy-based combinations (atezolizumab + bevacizumab; durvalumab + tremelimumab) as preferred first-line for advanced HCC; camrelizumab + rivoceranib is an additional option where available. The combination supported regulatory review in multiple regions.

References