Purpose
To assess the efficacy and safety of the anti-VEGF receptor-2 (VEGFR-2) antibody ramucirumab as first-line therapy in patients with advanced hepatocellular carcinoma and explore potential circulating biomarkers.
Experimental Design
Adults with advanced hepatocellular carcinoma and no prior systemic treatment received ramucirumab 8 mg/kg every two weeks until disease progression or limiting toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints included objective response rate (ORR) and overall survival (OS). Circulating biomarkers were evaluated before and after ramucirumab treatment in a subset of patients.
Results
Forty-two patients received ramucirumab. Median PFS was 4.0 months [95% confidence interval (CI), 2.6–5.7], ORR was 9.5% (95% CI, 2.7–22.6; 4/42 patients had apartial response), and median OS was 12.0 months (95% CI, 6.1–19.7). For patients with Barcelona Clinic Liver Cancer (BCLC) stage C disease, median OS was 4.4 months (95% CI, 0.5–9.0) for patients with Child-Pugh B cirrhosis versus 18.0 months (95% CI, 6.1–23.5) for patients with Child-Pugh A cirrhosis. Treatment-related grade ≥3 toxicities included hypertension (14%), gastrointestinal hemorrhage and infusion-related reactions (7% each), and fatigue (5%). There was one treatment-related death (gastrointestinal hemorrhage). After treatment with ramucirumab, there was an increase in serum VEGF and placental growth factor (PlGF) and a transient decrease in soluble VEGFR-2.
Conclusion
Ramucirumab monotherapy may confer anticancer activity in advanced hepatocellular carcinoma with an acceptable safety profile. Exploratory biomarker studies showed changes in circulating VEGF, PlGF, and sVEGFR-2 that are consistent with those seen with other anti-VEGF agents.
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