A phase II and biomarker study of ramucirumab, a human monoclonal antibody targeting the VEGF receptor-2, as first-line monotherapy in patients with advanced hepatocellular cancer.
Clin Cancer Res
; 19(23): 6614-23, 2013 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-24088738
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 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 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Biomarcadores de Tumor
/
Carcinoma Hepatocelular
/
Neoplasias Hepáticas
/
Anticuerpos Monoclonales
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Clin Cancer Res
Asunto de la revista:
NEOPLASIAS
Año:
2013
Tipo del documento:
Article
Pais de publicación:
Estados Unidos