In the phase 3 CARES-310 trial, 543 patients with unresectable hepatocellular carcinoma had a significant and clinically meaningful improvement in progression-free survival and overall survival with camrelizumab plus rivoceranib compared with sorafenib, researchers report. This dual therapy with an immune checkpoint inhibitor combined with an anti-angiogenic tyrosine kinase inhibitor (TKI) presents “a new and effective first-line treatment option for this population,” the authors conclude.
The international randomized, open-label, international study was conducted at 95 sites across 13 countries and regions worldwide. Patients with unresectable or metastatic hepatocellular carcinoma received either camrelizumab 200 mg intravenously every 2 weeks plus rivoceranib 250 mg orally once daily or sorafenib 400 mg orally twice daily. Based on primary endpoints of progression-free and overall survival, the study showed: “At the primary analysis for progression-free survival (May 10, 2021), median follow-up was 7.8 months (IQR 4.1–10.6). Median progression-free survival was significantly improved with camrelizumab–rivoceranib versus sorafenib (5.6 months [95% CI 5.5–6.3] vs 3.7 months [2.8–3.7]; hazard ratio [HR] 0.52 [95% CI 0.41–0.65]; one-sided P <0.0001). At the interim analysis for overall survival (Feb 8, 2022), median follow-up was 14.5 months (IQR 9.1–18.7). Median overall survival was significantly extended with camrelizumab–rivoceranib versus sorafenib (22.1 months [95% CI 19.1–27.2] vs 15.2 months [13.0–18.5]; HR 0.62 [95% CI 0.49–0.80]; one-sided P <0.0001). The most common grade 3 or 4 treatment-related adverse events were hypertension (102 [38%] of 272 patients in the camrelizumab–rivoceranib group vs 40 [15%] of 269 patients in the sorafenib group), palmar-plantar erythrodysaesthesia syndrome (33 [12%] vs 41 [15%]), increased aspartate aminotransferase (45 [17%] vs 14 [5%]), and increased alanine aminotransferase (35 [13%] vs eight [3%]). Treatment-related serious adverse events were reported in 66 (24%) patients in the camrelizumab–rivoceranib group and 16 (6%) in the sorafenib group. Treatment-related death occurred in two patients: one patient in the camrelizumab–rivoceranib group (ie, multiple organ dysfunction syndrome) and one patient in the sorafenib group (ie, respiratory failure and circulatory collapse).”