A Phase II and Biomarker Study of Ramucirumab, a Human Monoclonal Antibody Targeting the VEGF Receptor-2 in Patients with Advanced Hepatocellular Cancer
Mené sur 42 patients atteints d'un carcinome hépatocellulaire avancé, cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité du ramucirumab en traitement de première ligne
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 (HCC) and explore potential circulating biomarkers. Experimental Design: Adults with advanced HCC and no prior systemic treatment received ramucirumab 8 mg/kg/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% CI, 2.6-5.7], ORR was 9.5% [95% CI, 2.7-22.6] (4/42 patients had a partial 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 HCC 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.