Background: CARES-310 (NCT03764293) evaluated the combination of PD-1 inhibitor, camrelizumab (cam), and VEGFR-1-3 inhibitor, rivoceranib (rivo), compared to sorafenib (sor) for the treatment of uHCC. Cam + rivo significantly improved median overall survival (mOS) and median progression-free survival (mPFS) compared to sor (mOS, 23.8 months [mo] [95% CI 20.6, 27.2] vs 15.2 mo [95% CI 13.2, 18.5] hazard ratio [HR] 0.64 [95% CI 0.52, 0.79]; one-sided p<0.0001; mPFS, 5.6 mo [95% CI 5.5, 7.4] vs 3.7 mo [95% CI 3.1, 3.7]; HR 0.54 [95% CI 0.44, 0.67]; one-sided p<0.0001). The most common (≥10%) grade ≥3 treatment-related adverse events in the cam + rivo arm were hypertension (38.6%) and AST increased (20.2%).

Methods: A post-hoc analysis of CARES-310 was performed, where mOS and mPFS were estimated using the Kaplan-Meier method and compared between the 3 etiology groups of non-viral, hepatitis C virus (HCV), and hepatitis B virus (HBV) using the log-rank test.

Results: mOS was longer with camrelizumab plus rivoceranib compared with sorafenib in patients with non-viral (HR 0.68 [95% CI 0.39, 1.19]), HCV (HR 0.37 [95% CI 0.162, 0.84]), and HBV etiologies (HR 0.70 [95% CI 0.55, 0.89]) (Table). Similarly, mPFS was longer with camrelizumab plus rivoceranib compared with sorafenib in patients with non-viral (HR 0.55 [95% CI 0.34, 0.91]), HCV (HR 0.50 [95% CI 0.23, 1.06]), and HBV etiologies (HR 0.57 [95% CI 0.45, 0.72]) (Table).

Conclusions: Cam + rivo in CARES-310 suggested clinically meaningful mOS benefit in non-viral and viral HCC vs sor and provides assurance of clinical benefit for first line treatment to patients with uHCC independent of etiology.